US20040071712A1 - Modified peptides as therapeutic agents - Google Patents
Modified peptides as therapeutic agents Download PDFInfo
- Publication number
- US20040071712A1 US20040071712A1 US10/645,761 US64576103A US2004071712A1 US 20040071712 A1 US20040071712 A1 US 20040071712A1 US 64576103 A US64576103 A US 64576103A US 2004071712 A1 US2004071712 A1 US 2004071712A1
- Authority
- US
- United States
- Prior art keywords
- peptide
- seq
- sequence
- arg
- matter
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003814 drug Substances 0.000 title description 21
- 229940124597 therapeutic agent Drugs 0.000 title description 11
- 108091005601 modified peptides Proteins 0.000 title description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 430
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 159
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 122
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 238000000034 method Methods 0.000 claims abstract description 99
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 80
- 230000000694 effects Effects 0.000 claims abstract description 45
- 230000008569 process Effects 0.000 claims abstract description 39
- 241000588724 Escherichia coli Species 0.000 claims abstract description 37
- 238000002823 phage display Methods 0.000 claims abstract description 13
- 238000012216 screening Methods 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 239000002831 pharmacologic agent Substances 0.000 claims abstract description 4
- 239000005557 antagonist Substances 0.000 claims description 106
- 239000000203 mixture Substances 0.000 claims description 74
- 210000004027 cell Anatomy 0.000 claims description 66
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 47
- 108020004414 DNA Proteins 0.000 claims description 35
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 32
- 108010002352 Interleukin-1 Proteins 0.000 claims description 25
- 108010067902 Peptide Library Proteins 0.000 claims description 22
- 210000004899 c-terminal region Anatomy 0.000 claims description 17
- 229940124761 MMP inhibitor Drugs 0.000 claims description 15
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 11
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 11
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 150000007523 nucleic acids Chemical group 0.000 claims description 8
- 230000000295 complement effect Effects 0.000 claims description 7
- 238000004132 cross linking Methods 0.000 claims description 7
- 239000013604 expression vector Substances 0.000 claims description 6
- 125000001151 peptidyl group Chemical group 0.000 claims description 6
- 102000003675 cytokine receptors Human genes 0.000 claims description 3
- 108010057085 cytokine receptors Proteins 0.000 claims description 3
- 108010001857 Cell Surface Receptors Proteins 0.000 claims description 2
- 238000003752 polymerase chain reaction Methods 0.000 claims description 2
- 210000003705 ribosome Anatomy 0.000 claims description 2
- 231100000219 mutagenic Toxicity 0.000 claims 3
- 230000003505 mutagenic effect Effects 0.000 claims 3
- 108091033380 Coding strand Proteins 0.000 claims 2
- 102000006240 membrane receptors Human genes 0.000 claims 1
- 230000004927 fusion Effects 0.000 abstract description 63
- 150000001413 amino acids Chemical class 0.000 abstract description 42
- 238000001727 in vivo Methods 0.000 abstract description 14
- 238000002702 ribosome display Methods 0.000 abstract description 3
- 239000008177 pharmaceutical agent Substances 0.000 abstract 1
- 235000018102 proteins Nutrition 0.000 description 75
- 239000002773 nucleotide Substances 0.000 description 67
- 125000003729 nucleotide group Chemical group 0.000 description 67
- 229940024606 amino acid Drugs 0.000 description 57
- 230000027455 binding Effects 0.000 description 57
- 238000006243 chemical reaction Methods 0.000 description 57
- 235000001014 amino acid Nutrition 0.000 description 54
- 102000005962 receptors Human genes 0.000 description 47
- 108020003175 receptors Proteins 0.000 description 47
- 239000000539 dimer Substances 0.000 description 46
- 239000000047 product Substances 0.000 description 45
- 125000005647 linker group Chemical group 0.000 description 41
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 38
- 229920001223 polyethylene glycol Polymers 0.000 description 38
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 35
- 239000002202 Polyethylene glycol Substances 0.000 description 35
- 101710112672 Probable tape measure protein Proteins 0.000 description 35
- 101710204224 Tape measure protein Proteins 0.000 description 35
- 239000003981 vehicle Substances 0.000 description 35
- 239000000178 monomer Substances 0.000 description 31
- BYXHQQCXAJARLQ-ZLUOBGJFSA-N Ala-Ala-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O BYXHQQCXAJARLQ-ZLUOBGJFSA-N 0.000 description 30
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 29
- -1 polyethylene Polymers 0.000 description 29
- 241000699670 Mus sp. Species 0.000 description 28
- 238000009472 formulation Methods 0.000 description 28
- 108091034117 Oligonucleotide Proteins 0.000 description 27
- 210000001772 blood platelet Anatomy 0.000 description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- 108010077515 glycylproline Proteins 0.000 description 26
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 25
- 108010080629 tryptophan-leucine Proteins 0.000 description 24
- 108010051242 phenylalanylserine Proteins 0.000 description 23
- 230000001225 therapeutic effect Effects 0.000 description 23
- 239000013598 vector Substances 0.000 description 23
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 22
- 102100040247 Tumor necrosis factor Human genes 0.000 description 22
- 108010087924 alanylproline Proteins 0.000 description 22
- 239000003446 ligand Substances 0.000 description 22
- HHGYNJRJIINWAK-FXQIFTODSA-N Ala-Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N HHGYNJRJIINWAK-FXQIFTODSA-N 0.000 description 21
- 241000282326 Felis catus Species 0.000 description 20
- 102000000589 Interleukin-1 Human genes 0.000 description 20
- 102000037865 fusion proteins Human genes 0.000 description 20
- 108020001507 fusion proteins Proteins 0.000 description 20
- 108010077112 prolyl-proline Proteins 0.000 description 20
- FDMCIBSQRKFSTJ-RHYQMDGZSA-N Pro-Thr-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O FDMCIBSQRKFSTJ-RHYQMDGZSA-N 0.000 description 19
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 19
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 19
- 102100031939 Erythropoietin Human genes 0.000 description 18
- JDMKQHSHKJHAHR-UHFFFAOYSA-N Phe-Phe-Leu-Tyr Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)CC1=CC=CC=C1 JDMKQHSHKJHAHR-UHFFFAOYSA-N 0.000 description 18
- IHCXPSYCHXFXKT-DCAQKATOSA-N Pro-Arg-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O IHCXPSYCHXFXKT-DCAQKATOSA-N 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 108010092408 Eosinophil Peroxidase Proteins 0.000 description 17
- MTFVYKQRLXYAQN-LAEOZQHASA-N Ile-Glu-Gly Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O MTFVYKQRLXYAQN-LAEOZQHASA-N 0.000 description 17
- 108010052670 arginyl-glutamyl-glutamic acid Proteins 0.000 description 17
- 108010047857 aspartylglycine Proteins 0.000 description 17
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 17
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 17
- BQBPFMNVOWDLHO-XIRDDKMYSA-N Arg-Gln-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N BQBPFMNVOWDLHO-XIRDDKMYSA-N 0.000 description 16
- 101100512078 Caenorhabditis elegans lys-1 gene Proteins 0.000 description 16
- 241000880493 Leptailurus serval Species 0.000 description 16
- YCJCEMKOZOYBEF-OEAJRASXSA-N Lys-Thr-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O YCJCEMKOZOYBEF-OEAJRASXSA-N 0.000 description 16
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 16
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 16
- 230000000692 anti-sense effect Effects 0.000 description 16
- 238000003556 assay Methods 0.000 description 16
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 16
- 238000005516 engineering process Methods 0.000 description 16
- 230000003993 interaction Effects 0.000 description 16
- 108010031719 prolyl-serine Proteins 0.000 description 16
- 108091008146 restriction endonucleases Proteins 0.000 description 16
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 16
- ALTQTAKGRFLRLR-GUBZILKMSA-N Cys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N ALTQTAKGRFLRLR-GUBZILKMSA-N 0.000 description 15
- 239000004471 Glycine Substances 0.000 description 15
- 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 15
- 102100034195 Thrombopoietin Human genes 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 108010064235 lysylglycine Proteins 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- 239000013612 plasmid Substances 0.000 description 15
- BVLIJXXSXBUGEC-SRVKXCTJSA-N Asn-Asn-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BVLIJXXSXBUGEC-SRVKXCTJSA-N 0.000 description 14
- WQLJRNRLHWJIRW-KKUMJFAQSA-N Asn-His-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)N)N)O WQLJRNRLHWJIRW-KKUMJFAQSA-N 0.000 description 14
- RCFGLXMZDYNRSC-CIUDSAMLSA-N Asn-Lys-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O RCFGLXMZDYNRSC-CIUDSAMLSA-N 0.000 description 14
- HMIXCETWRYDVMO-GUBZILKMSA-N Gln-Pro-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O HMIXCETWRYDVMO-GUBZILKMSA-N 0.000 description 14
- NJCALAAIGREHDR-WDCWCFNPSA-N Glu-Leu-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NJCALAAIGREHDR-WDCWCFNPSA-N 0.000 description 14
- AAJHGGDRKHYSDH-GUBZILKMSA-N Glu-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O AAJHGGDRKHYSDH-GUBZILKMSA-N 0.000 description 14
- WGYHAAXZWPEBDQ-IFFSRLJSSA-N Glu-Val-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGYHAAXZWPEBDQ-IFFSRLJSSA-N 0.000 description 14
- JSLVAHYTAJJEQH-QWRGUYRKSA-N Gly-Ser-Phe Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JSLVAHYTAJJEQH-QWRGUYRKSA-N 0.000 description 14
- BKTXKJMNTSMJDQ-AVGNSLFASA-N Leu-His-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N BKTXKJMNTSMJDQ-AVGNSLFASA-N 0.000 description 14
- UHNQRAFSEBGZFZ-YESZJQIVSA-N Leu-Phe-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N UHNQRAFSEBGZFZ-YESZJQIVSA-N 0.000 description 14
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 14
- AIQWYVFNBNNOLU-RHYQMDGZSA-N Leu-Thr-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O AIQWYVFNBNNOLU-RHYQMDGZSA-N 0.000 description 14
- WSXTWLJHTLRFLW-SRVKXCTJSA-N Lys-Ala-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O WSXTWLJHTLRFLW-SRVKXCTJSA-N 0.000 description 14
- ODTZHNZPINULEU-KKUMJFAQSA-N Lys-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N ODTZHNZPINULEU-KKUMJFAQSA-N 0.000 description 14
- GILLQRYAWOMHED-DCAQKATOSA-N Lys-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN GILLQRYAWOMHED-DCAQKATOSA-N 0.000 description 14
- ZPPVJIJMIKTERM-YUMQZZPRSA-N Pro-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]1CCCN1 ZPPVJIJMIKTERM-YUMQZZPRSA-N 0.000 description 14
- ULWBBFKQBDNGOY-RWMBFGLXSA-N Pro-Lys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@@H]2C(=O)O ULWBBFKQBDNGOY-RWMBFGLXSA-N 0.000 description 14
- UEJYSALTSUZXFV-SRVKXCTJSA-N Rigin Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O UEJYSALTSUZXFV-SRVKXCTJSA-N 0.000 description 14
- QEDMOZUJTGEIBF-FXQIFTODSA-N Ser-Arg-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O QEDMOZUJTGEIBF-FXQIFTODSA-N 0.000 description 14
- LAFLAXHTDVNVEL-WDCWCFNPSA-N Thr-Gln-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N)O LAFLAXHTDVNVEL-WDCWCFNPSA-N 0.000 description 14
- AMXMBCAXAZUCFA-RHYQMDGZSA-N Thr-Leu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMXMBCAXAZUCFA-RHYQMDGZSA-N 0.000 description 14
- SSSDKJMQMZTMJP-BVSLBCMMSA-N Trp-Tyr-Val Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CC=C(O)C=C1 SSSDKJMQMZTMJP-BVSLBCMMSA-N 0.000 description 14
- XIFAHCUNWWKUDE-DCAQKATOSA-N Val-Cys-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O)N XIFAHCUNWWKUDE-DCAQKATOSA-N 0.000 description 14
- BGTDGENDNWGMDQ-KJEVXHAQSA-N Val-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C(C)C)N)O BGTDGENDNWGMDQ-KJEVXHAQSA-N 0.000 description 14
- 108010038633 aspartylglutamate Proteins 0.000 description 14
- 108010051110 tyrosyl-lysine Proteins 0.000 description 14
- OINVDEKBKBCPLX-JXUBOQSCSA-N Ala-Lys-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OINVDEKBKBCPLX-JXUBOQSCSA-N 0.000 description 13
- HNXWVVHIGTZTBO-LKXGYXEUSA-N Asn-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O HNXWVVHIGTZTBO-LKXGYXEUSA-N 0.000 description 13
- KBQOUDLMWYWXNP-YDHLFZDLSA-N Asn-Val-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CC(=O)N)N KBQOUDLMWYWXNP-YDHLFZDLSA-N 0.000 description 13
- SAEVTQWAYDPXMU-KATARQTJSA-N Cys-Thr-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O SAEVTQWAYDPXMU-KATARQTJSA-N 0.000 description 13
- NVEASDQHBRZPSU-BQBZGAKWSA-N Gln-Gln-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O NVEASDQHBRZPSU-BQBZGAKWSA-N 0.000 description 13
- HUFCEIHAFNVSNR-IHRRRGAJSA-N Glu-Gln-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HUFCEIHAFNVSNR-IHRRRGAJSA-N 0.000 description 13
- NPLGQVKZFGJWAI-QWHCGFSZSA-N Phe-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O NPLGQVKZFGJWAI-QWHCGFSZSA-N 0.000 description 13
- COLJZWUVZIXSSS-CIUDSAMLSA-N Ser-Cys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N COLJZWUVZIXSSS-CIUDSAMLSA-N 0.000 description 13
- 101710113649 Thyroid peroxidase Proteins 0.000 description 13
- QYSBJAUCUKHSLU-JYJNAYRXSA-N Tyr-Arg-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O QYSBJAUCUKHSLU-JYJNAYRXSA-N 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 108010015792 glycyllysine Proteins 0.000 description 13
- 108010070643 prolylglutamic acid Proteins 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 108010073969 valyllysine Proteins 0.000 description 13
- DPNZTBKGAUAZQU-DLOVCJGASA-N Ala-Leu-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N DPNZTBKGAUAZQU-DLOVCJGASA-N 0.000 description 12
- ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-N 0.000 description 12
- FTNRWCPWDWRPAV-BZSNNMDCSA-N Asn-Phe-Phe Chemical compound C([C@H](NC(=O)[C@H](CC(N)=O)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 FTNRWCPWDWRPAV-BZSNNMDCSA-N 0.000 description 12
- CUQDCPXNZPDYFQ-ZLUOBGJFSA-N Asp-Ser-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O CUQDCPXNZPDYFQ-ZLUOBGJFSA-N 0.000 description 12
- OHLLDUNVMPPUMD-DCAQKATOSA-N Cys-Leu-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N OHLLDUNVMPPUMD-DCAQKATOSA-N 0.000 description 12
- NEDQVOQDDBCRGG-UHFFFAOYSA-N Gly Gly Thr Tyr Chemical compound NCC(=O)NCC(=O)NC(C(O)C)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 NEDQVOQDDBCRGG-UHFFFAOYSA-N 0.000 description 12
- BUEFQXUHTUZXHR-LURJTMIESA-N Gly-Gly-Pro zwitterion Chemical compound NCC(=O)NCC(=O)N1CCC[C@H]1C(O)=O BUEFQXUHTUZXHR-LURJTMIESA-N 0.000 description 12
- GMTXWRIDLGTVFC-IUCAKERBSA-N Gly-Lys-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GMTXWRIDLGTVFC-IUCAKERBSA-N 0.000 description 12
- GLACUWHUYFBSPJ-FJXKBIBVSA-N Gly-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GLACUWHUYFBSPJ-FJXKBIBVSA-N 0.000 description 12
- DFJJAVZIHDFOGQ-MNXVOIDGSA-N Ile-Glu-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N DFJJAVZIHDFOGQ-MNXVOIDGSA-N 0.000 description 12
- SBANPBVRHYIMRR-UHFFFAOYSA-N Leu-Ser-Pro Natural products CC(C)CC(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O SBANPBVRHYIMRR-UHFFFAOYSA-N 0.000 description 12
- RNYLNYTYMXACRI-VFAJRCTISA-N Leu-Thr-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O RNYLNYTYMXACRI-VFAJRCTISA-N 0.000 description 12
- RKIIYGUHIQJCBW-SRVKXCTJSA-N Met-His-Glu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O RKIIYGUHIQJCBW-SRVKXCTJSA-N 0.000 description 12
- FWAHLGXNBLWIKB-NAKRPEOUSA-N Met-Ile-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCSC FWAHLGXNBLWIKB-NAKRPEOUSA-N 0.000 description 12
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 12
- CGBYDGAJHSOGFQ-LPEHRKFASA-N Pro-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 CGBYDGAJHSOGFQ-LPEHRKFASA-N 0.000 description 12
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 12
- VAUMZJHYZQXZBQ-WHFBIAKZSA-N Ser-Asn-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O VAUMZJHYZQXZBQ-WHFBIAKZSA-N 0.000 description 12
- MUJQWSAWLLRJCE-KATARQTJSA-N Ser-Leu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MUJQWSAWLLRJCE-KATARQTJSA-N 0.000 description 12
- HNDMFDBQXYZSRM-IHRRRGAJSA-N Ser-Val-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HNDMFDBQXYZSRM-IHRRRGAJSA-N 0.000 description 12
- SXAGUVRFGJSFKC-ZEILLAHLSA-N Thr-His-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SXAGUVRFGJSFKC-ZEILLAHLSA-N 0.000 description 12
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 12
- GZUIDWDVMWZSMI-KKUMJFAQSA-N Tyr-Lys-Cys Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CS)C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GZUIDWDVMWZSMI-KKUMJFAQSA-N 0.000 description 12
- OACSGBOREVRSME-NHCYSSNCSA-N Val-His-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(N)=O)C(O)=O OACSGBOREVRSME-NHCYSSNCSA-N 0.000 description 12
- NZYNRRGJJVSSTJ-GUBZILKMSA-N Val-Ser-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NZYNRRGJJVSSTJ-GUBZILKMSA-N 0.000 description 12
- 108010049041 glutamylalanine Proteins 0.000 description 12
- 108010010147 glycylglutamine Proteins 0.000 description 12
- 230000002401 inhibitory effect Effects 0.000 description 12
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 12
- 210000003593 megakaryocyte Anatomy 0.000 description 12
- 108010073101 phenylalanylleucine Proteins 0.000 description 12
- 108010080244 somatostatin(3-6) Proteins 0.000 description 12
- 108010043680 somatostatin(7-10) Proteins 0.000 description 12
- 108010052774 valyl-lysyl-glycyl-phenylalanyl-tyrosine Proteins 0.000 description 12
- WSGVTKZFVJSJOG-RCOVLWMOSA-N Asp-Gly-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O WSGVTKZFVJSJOG-RCOVLWMOSA-N 0.000 description 11
- YUELDQUPTAYEGM-XIRDDKMYSA-N Asp-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)O)N YUELDQUPTAYEGM-XIRDDKMYSA-N 0.000 description 11
- SMEYEQDCCBHTEF-FXQIFTODSA-N Cys-Pro-Ala Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O SMEYEQDCCBHTEF-FXQIFTODSA-N 0.000 description 11
- KSMSFCBQBQPFAD-GUBZILKMSA-N Cys-Pro-Pro Chemical compound SC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 KSMSFCBQBQPFAD-GUBZILKMSA-N 0.000 description 11
- 229920002307 Dextran Polymers 0.000 description 11
- OPAINBJQDQTGJY-JGVFFNPUSA-N Glu-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCC(=O)O)N)C(=O)O OPAINBJQDQTGJY-JGVFFNPUSA-N 0.000 description 11
- BPCLDCNZBUYGOD-BPUTZDHNSA-N Glu-Trp-Glu Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 BPCLDCNZBUYGOD-BPUTZDHNSA-N 0.000 description 11
- WMIOEVKKYIMVKI-DCAQKATOSA-N Leu-Pro-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WMIOEVKKYIMVKI-DCAQKATOSA-N 0.000 description 11
- YKIRNDPUWONXQN-GUBZILKMSA-N Lys-Asn-Gln Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YKIRNDPUWONXQN-GUBZILKMSA-N 0.000 description 11
- KWUKZRFFKPLUPE-HJGDQZAQSA-N Lys-Asp-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KWUKZRFFKPLUPE-HJGDQZAQSA-N 0.000 description 11
- CAVRAQIDHUPECU-UVOCVTCTSA-N Lys-Thr-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAVRAQIDHUPECU-UVOCVTCTSA-N 0.000 description 11
- SJRQWEDYTKYHHL-SLFFLAALSA-N Phe-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O SJRQWEDYTKYHHL-SLFFLAALSA-N 0.000 description 11
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 11
- VPEVBAUSTBWQHN-NHCYSSNCSA-N Pro-Glu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O VPEVBAUSTBWQHN-NHCYSSNCSA-N 0.000 description 11
- HZWAHWQZPSXNCB-BPUTZDHNSA-N Ser-Arg-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O HZWAHWQZPSXNCB-BPUTZDHNSA-N 0.000 description 11
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 11
- XUDRHBPSPAPDJP-SRVKXCTJSA-N Ser-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO XUDRHBPSPAPDJP-SRVKXCTJSA-N 0.000 description 11
- RHAPJNVNWDBFQI-BQBZGAKWSA-N Ser-Pro-Gly Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O RHAPJNVNWDBFQI-BQBZGAKWSA-N 0.000 description 11
- 108700005078 Synthetic Genes Proteins 0.000 description 11
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 11
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 11
- BMGOFDMKDVVGJG-NHCYSSNCSA-N Val-Asp-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N BMGOFDMKDVVGJG-NHCYSSNCSA-N 0.000 description 11
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 11
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 11
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 11
- 108010071097 threonyl-lysyl-proline Proteins 0.000 description 11
- XJFPXLWGZWAWRQ-UHFFFAOYSA-N 2-[[2-[[2-[[2-[[2-[(2-azaniumylacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]acetate Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(O)=O XJFPXLWGZWAWRQ-UHFFFAOYSA-N 0.000 description 10
- JQFJNGVSGOUQDH-XIRDDKMYSA-N Arg-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCN=C(N)N)N)C(O)=O)=CNC2=C1 JQFJNGVSGOUQDH-XIRDDKMYSA-N 0.000 description 10
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 10
- WGBMNLCRYKSWAR-DCAQKATOSA-N Met-Asp-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN WGBMNLCRYKSWAR-DCAQKATOSA-N 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 10
- MOVJSUIKUNCVMG-ZLUOBGJFSA-N Ser-Cys-Ser Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O)N)O MOVJSUIKUNCVMG-ZLUOBGJFSA-N 0.000 description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 108010013835 arginine glutamate Proteins 0.000 description 10
- 108010060199 cysteinylproline Proteins 0.000 description 10
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 10
- 108010092114 histidylphenylalanine Proteins 0.000 description 10
- 210000003000 inclusion body Anatomy 0.000 description 10
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 9
- XIZWKXATMJODQW-KKUMJFAQSA-N Cys-His-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CS)N XIZWKXATMJODQW-KKUMJFAQSA-N 0.000 description 9
- SDTPKSOWFXBACN-GUBZILKMSA-N His-Glu-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O SDTPKSOWFXBACN-GUBZILKMSA-N 0.000 description 9
- CYCGARJWIQWPQM-YJRXYDGGSA-N Thr-Tyr-Ser Chemical compound C[C@@H](O)[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CO)C([O-])=O)CC1=CC=C(O)C=C1 CYCGARJWIQWPQM-YJRXYDGGSA-N 0.000 description 9
- 102000003970 Vinculin Human genes 0.000 description 9
- 108090000384 Vinculin Proteins 0.000 description 9
- 108010092854 aspartyllysine Proteins 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000006471 dimerization reaction Methods 0.000 description 9
- 108010078144 glutaminyl-glycine Proteins 0.000 description 9
- 229920000642 polymer Polymers 0.000 description 9
- 229920001184 polypeptide Polymers 0.000 description 9
- 239000004094 surface-active agent Substances 0.000 description 9
- RCGFMNKLEKXILD-XYCLDAKMSA-N (2s,3r)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-amino-3-phenylpropanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]hexanoyl]amino]-3-hydroxybutanoic acid Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@H](O)C)C(O)=O)C1=CC=CC=C1 RCGFMNKLEKXILD-XYCLDAKMSA-N 0.000 description 8
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 8
- CNKAZIGBGQIHLL-GUBZILKMSA-N Asp-Arg-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N CNKAZIGBGQIHLL-GUBZILKMSA-N 0.000 description 8
- IIMZHVKZBGSEKZ-SZMVWBNQSA-N Gln-Trp-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(O)=O IIMZHVKZBGSEKZ-SZMVWBNQSA-N 0.000 description 8
- HFPVRZWORNJRRC-UWVGGRQHSA-N Gly-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN HFPVRZWORNJRRC-UWVGGRQHSA-N 0.000 description 8
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 8
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 8
- RCFDOSNHHZGBOY-UHFFFAOYSA-N L-isoleucyl-L-alanine Natural products CCC(C)C(N)C(=O)NC(C)C(O)=O RCFDOSNHHZGBOY-UHFFFAOYSA-N 0.000 description 8
- GRZSCTXVCDUIPO-SRVKXCTJSA-N Leu-Arg-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O GRZSCTXVCDUIPO-SRVKXCTJSA-N 0.000 description 8
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 8
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 8
- ZGVYWHODYWRPLK-GUBZILKMSA-N Met-Pro-Cys Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(O)=O ZGVYWHODYWRPLK-GUBZILKMSA-N 0.000 description 8
- QPFJSHSJFIYDJZ-GHCJXIJMSA-N Ser-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO QPFJSHSJFIYDJZ-GHCJXIJMSA-N 0.000 description 8
- VFWQQZMRKFOGLE-ZLUOBGJFSA-N Ser-Ser-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)O VFWQQZMRKFOGLE-ZLUOBGJFSA-N 0.000 description 8
- NBIIPOKZPUGATB-BWBBJGPYSA-N Thr-Ser-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)O NBIIPOKZPUGATB-BWBBJGPYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 230000004071 biological effect Effects 0.000 description 8
- 150000001720 carbohydrates Chemical class 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 108010089804 glycyl-threonine Proteins 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 206010043554 thrombocytopenia Diseases 0.000 description 8
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 8
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 8
- NDNZRWUDUMTITL-FXQIFTODSA-N Cys-Ser-Val Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NDNZRWUDUMTITL-FXQIFTODSA-N 0.000 description 7
- HGJREIGJLUQBTJ-SZMVWBNQSA-N Glu-Trp-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(O)=O HGJREIGJLUQBTJ-SZMVWBNQSA-N 0.000 description 7
- SYOJVRNQCXYEOV-XVKPBYJWSA-N Gly-Val-Glu Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SYOJVRNQCXYEOV-XVKPBYJWSA-N 0.000 description 7
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 7
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 7
- 108010065920 Insulin Lispro Proteins 0.000 description 7
- SBANPBVRHYIMRR-GARJFASQSA-N Leu-Ser-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N SBANPBVRHYIMRR-GARJFASQSA-N 0.000 description 7
- XDMMOISUAHXXFD-SRVKXCTJSA-N Phe-Ser-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O XDMMOISUAHXXFD-SRVKXCTJSA-N 0.000 description 7
- SBJCTAZFSZXWSR-AVGNSLFASA-N Val-Met-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N SBJCTAZFSZXWSR-AVGNSLFASA-N 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 108010047495 alanylglycine Proteins 0.000 description 7
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 7
- 235000018417 cysteine Nutrition 0.000 description 7
- 230000007812 deficiency Effects 0.000 description 7
- 239000003085 diluting agent Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- XVZCXCTYGHPNEM-IHRRRGAJSA-N (2s)-1-[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O XVZCXCTYGHPNEM-IHRRRGAJSA-N 0.000 description 6
- VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 6
- DXQIQUIQYAGRCC-CIUDSAMLSA-N Arg-Asp-Gln Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)CN=C(N)N DXQIQUIQYAGRCC-CIUDSAMLSA-N 0.000 description 6
- SRUUBQBAVNQZGJ-LAEOZQHASA-N Asn-Gln-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)N SRUUBQBAVNQZGJ-LAEOZQHASA-N 0.000 description 6
- OLVIPTLKNSAYRJ-YUMQZZPRSA-N Asn-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N OLVIPTLKNSAYRJ-YUMQZZPRSA-N 0.000 description 6
- JSNWZMFSLIWAHS-HJGDQZAQSA-N Asp-Thr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O JSNWZMFSLIWAHS-HJGDQZAQSA-N 0.000 description 6
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 description 6
- ZALGPUWUVHOGAE-GVXVVHGQSA-N Glu-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZALGPUWUVHOGAE-GVXVVHGQSA-N 0.000 description 6
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 6
- VWHGTYCRDRBSFI-ZETCQYMHSA-N Leu-Gly-Gly Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)NCC(O)=O VWHGTYCRDRBSFI-ZETCQYMHSA-N 0.000 description 6
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 6
- AUNMOHYWTAPQLA-XUXIUFHCSA-N Leu-Met-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O AUNMOHYWTAPQLA-XUXIUFHCSA-N 0.000 description 6
- OIQSIMFSVLLWBX-VOAKCMCISA-N Lys-Leu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OIQSIMFSVLLWBX-VOAKCMCISA-N 0.000 description 6
- SVSQSPICRKBMSZ-SRVKXCTJSA-N Lys-Pro-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O SVSQSPICRKBMSZ-SRVKXCTJSA-N 0.000 description 6
- KWMUAKQOVYCQJQ-ZPFDUUQYSA-N Pro-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@@H]1CCCN1 KWMUAKQOVYCQJQ-ZPFDUUQYSA-N 0.000 description 6
- HWLKHNDRXWTFTN-GUBZILKMSA-N Pro-Pro-Cys Chemical compound C1C[C@H](NC1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CS)C(=O)O HWLKHNDRXWTFTN-GUBZILKMSA-N 0.000 description 6
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 6
- OYEDZGNMSBZCIM-XGEHTFHBSA-N Ser-Arg-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OYEDZGNMSBZCIM-XGEHTFHBSA-N 0.000 description 6
- HMRAQFJFTOLDKW-GUBZILKMSA-N Ser-His-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O HMRAQFJFTOLDKW-GUBZILKMSA-N 0.000 description 6
- ZESGVALRVJIVLZ-VFCFLDTKSA-N Thr-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O ZESGVALRVJIVLZ-VFCFLDTKSA-N 0.000 description 6
- KAFKKRJQHOECGW-JCOFBHIZSA-N Thr-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)[C@H](O)C)C(O)=O)=CNC2=C1 KAFKKRJQHOECGW-JCOFBHIZSA-N 0.000 description 6
- FYBFTPLPAXZBOY-KKHAAJSZSA-N Thr-Val-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O FYBFTPLPAXZBOY-KKHAAJSZSA-N 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- XGFGVFMXDXALEV-XIRDDKMYSA-N Trp-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N XGFGVFMXDXALEV-XIRDDKMYSA-N 0.000 description 6
- CYLQUSBOSWCHTO-BPUTZDHNSA-N Trp-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N CYLQUSBOSWCHTO-BPUTZDHNSA-N 0.000 description 6
- VHIZXDZMTDVFGX-DCAQKATOSA-N Val-Ser-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N VHIZXDZMTDVFGX-DCAQKATOSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000001093 anti-cancer Effects 0.000 description 6
- 108010008355 arginyl-glutamine Proteins 0.000 description 6
- 108010068265 aspartyltyrosine Proteins 0.000 description 6
- 235000014633 carbohydrates Nutrition 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 6
- 108010069495 cysteinyltyrosine Proteins 0.000 description 6
- 239000007884 disintegrant Substances 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 description 6
- 230000013595 glycosylation Effects 0.000 description 6
- 238000006206 glycosylation reaction Methods 0.000 description 6
- 108010051307 glycyl-glycyl-proline Proteins 0.000 description 6
- 210000003630 histaminocyte Anatomy 0.000 description 6
- 230000002209 hydrophobic effect Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 108010091871 leucylmethionine Proteins 0.000 description 6
- 235000018977 lysine Nutrition 0.000 description 6
- 150000002482 oligosaccharides Chemical class 0.000 description 6
- 230000003204 osmotic effect Effects 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- ODWSTKXGQGYHSH-FXQIFTODSA-N Ala-Arg-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O ODWSTKXGQGYHSH-FXQIFTODSA-N 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- AHWRSSLYSGLBGD-CIUDSAMLSA-N Asp-Pro-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AHWRSSLYSGLBGD-CIUDSAMLSA-N 0.000 description 5
- 102100037084 C4b-binding protein alpha chain Human genes 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 150000008574 D-amino acids Chemical class 0.000 description 5
- 102100021758 E3 ubiquitin-protein transferase MAEA Human genes 0.000 description 5
- ITYRYNUZHPNCIK-GUBZILKMSA-N Glu-Ala-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O ITYRYNUZHPNCIK-GUBZILKMSA-N 0.000 description 5
- HNVFSTLPVJWIDV-CIUDSAMLSA-N Glu-Glu-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HNVFSTLPVJWIDV-CIUDSAMLSA-N 0.000 description 5
- ALMBZBOCGSVSAI-ACZMJKKPSA-N Glu-Ser-Asn Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ALMBZBOCGSVSAI-ACZMJKKPSA-N 0.000 description 5
- MFYLRRCYBBJYPI-JYJNAYRXSA-N Glu-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O MFYLRRCYBBJYPI-JYJNAYRXSA-N 0.000 description 5
- WKJKBELXHCTHIJ-WPRPVWTQSA-N Gly-Arg-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N WKJKBELXHCTHIJ-WPRPVWTQSA-N 0.000 description 5
- PDUHNKAFQXQNLH-ZETCQYMHSA-N Gly-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)NCC(O)=O PDUHNKAFQXQNLH-ZETCQYMHSA-N 0.000 description 5
- WCORRBXVISTKQL-WHFBIAKZSA-N Gly-Ser-Ser Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WCORRBXVISTKQL-WHFBIAKZSA-N 0.000 description 5
- 101000740689 Homo sapiens C4b-binding protein beta chain Proteins 0.000 description 5
- MKWSZEHGHSLNPF-NAKRPEOUSA-N Ile-Ala-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O)N MKWSZEHGHSLNPF-NAKRPEOUSA-N 0.000 description 5
- 108010002386 Interleukin-3 Proteins 0.000 description 5
- 102000000646 Interleukin-3 Human genes 0.000 description 5
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 5
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 5
- ISHNZELVUVPCHY-ZETCQYMHSA-N Lys-Gly-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O ISHNZELVUVPCHY-ZETCQYMHSA-N 0.000 description 5
- WQDKIVRHTQYJSN-DCAQKATOSA-N Lys-Ser-Arg Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N WQDKIVRHTQYJSN-DCAQKATOSA-N 0.000 description 5
- DLCAXBGXGOVUCD-PPCPHDFISA-N Lys-Thr-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DLCAXBGXGOVUCD-PPCPHDFISA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 5
- PRKWBYCXBBSLSK-GUBZILKMSA-N Pro-Ser-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O PRKWBYCXBBSLSK-GUBZILKMSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- ASJDFGOPDCVXTG-KATARQTJSA-N Thr-Cys-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O ASJDFGOPDCVXTG-KATARQTJSA-N 0.000 description 5
- JNKAYADBODLPMQ-HSHDSVGOSA-N Thr-Trp-Val Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)[C@@H](C)O)=CNC2=C1 JNKAYADBODLPMQ-HSHDSVGOSA-N 0.000 description 5
- BEZTUFWTPVOROW-KJEVXHAQSA-N Thr-Tyr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O BEZTUFWTPVOROW-KJEVXHAQSA-N 0.000 description 5
- CXPJPTFWKXNDKV-NUTKFTJISA-N Trp-Leu-Ala Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O)=CNC2=C1 CXPJPTFWKXNDKV-NUTKFTJISA-N 0.000 description 5
- SCCKSNREWHMKOJ-SRVKXCTJSA-N Tyr-Asn-Ser Chemical compound N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O SCCKSNREWHMKOJ-SRVKXCTJSA-N 0.000 description 5
- RKIGNDAHUOOIMJ-BQFCYCMXSA-N Val-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 RKIGNDAHUOOIMJ-BQFCYCMXSA-N 0.000 description 5
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 239000002158 endotoxin Substances 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 102000006495 integrins Human genes 0.000 description 5
- 108010044426 integrins Proteins 0.000 description 5
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 5
- 229920006008 lipopolysaccharide Polymers 0.000 description 5
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
- 230000003278 mimic effect Effects 0.000 description 5
- 229920001542 oligosaccharide Polymers 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 108010048818 seryl-histidine Proteins 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 229940032147 starch Drugs 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 5
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 4
- IFMZMDAHXSSNLT-QAETUUGQSA-N (2s)-2-[[(2s)-4-amino-2-[[(2s)-6-amino-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]amino]-3-phenylpropanoic acid Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IFMZMDAHXSSNLT-QAETUUGQSA-N 0.000 description 4
- KWTVWJPNHAOREN-IHRRRGAJSA-N Arg-Asn-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O KWTVWJPNHAOREN-IHRRRGAJSA-N 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 4
- SLKLLQWZQHXYSV-CIUDSAMLSA-N Asn-Ala-Lys Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O SLKLLQWZQHXYSV-CIUDSAMLSA-N 0.000 description 4
- KTTCQQNRRLCIBC-GHCJXIJMSA-N Asp-Ile-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O KTTCQQNRRLCIBC-GHCJXIJMSA-N 0.000 description 4
- 102100030009 Azurocidin Human genes 0.000 description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
- PRVVCRZLTJNPCS-FXQIFTODSA-N Cys-Arg-Asn Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N PRVVCRZLTJNPCS-FXQIFTODSA-N 0.000 description 4
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- 239000001856 Ethyl cellulose Substances 0.000 description 4
- DRDSQGHKTLSNEA-GLLZPBPUSA-N Gln-Glu-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DRDSQGHKTLSNEA-GLLZPBPUSA-N 0.000 description 4
- XKBASPWPBXNVLQ-WDSKDSINSA-N Gln-Gly-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O XKBASPWPBXNVLQ-WDSKDSINSA-N 0.000 description 4
- NKLRYVLERDYDBI-FXQIFTODSA-N Glu-Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NKLRYVLERDYDBI-FXQIFTODSA-N 0.000 description 4
- XMPXVJIDADUOQB-RCOVLWMOSA-N Gly-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C([O-])=O)NC(=O)CNC(=O)C[NH3+] XMPXVJIDADUOQB-RCOVLWMOSA-N 0.000 description 4
- HZWWOGWOBQBETJ-CUJWVEQBSA-N His-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N)O HZWWOGWOBQBETJ-CUJWVEQBSA-N 0.000 description 4
- 101000793686 Homo sapiens Azurocidin Proteins 0.000 description 4
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 4
- 108090000174 Interleukin-10 Proteins 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 102000016267 Leptin Human genes 0.000 description 4
- 108010092277 Leptin Proteins 0.000 description 4
- ZGGVHTQAPHVMKM-IHPCNDPISA-N Leu-Trp-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CCCCN)C(=O)O)N ZGGVHTQAPHVMKM-IHPCNDPISA-N 0.000 description 4
- PBLLTSKBTAHDNA-KBPBESRZSA-N Lys-Gly-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PBLLTSKBTAHDNA-KBPBESRZSA-N 0.000 description 4
- AFLBTVGQCQLOFJ-AVGNSLFASA-N Lys-Pro-Arg Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O AFLBTVGQCQLOFJ-AVGNSLFASA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- UZWMJZSOXGOVIN-LURJTMIESA-N Met-Gly-Gly Chemical compound CSCC[C@H](N)C(=O)NCC(=O)NCC(O)=O UZWMJZSOXGOVIN-LURJTMIESA-N 0.000 description 4
- QGRJTULYDZUBAY-ZPFDUUQYSA-N Met-Ile-Glu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O QGRJTULYDZUBAY-ZPFDUUQYSA-N 0.000 description 4
- YMTMNYNEZDAGMW-RNXOBYDBSA-N Phe-Phe-Trp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O)N YMTMNYNEZDAGMW-RNXOBYDBSA-N 0.000 description 4
- MCIXMYKSPQUMJG-SRVKXCTJSA-N Phe-Ser-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MCIXMYKSPQUMJG-SRVKXCTJSA-N 0.000 description 4
- GNRMAQSIROFNMI-IXOXFDKPSA-N Phe-Thr-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O GNRMAQSIROFNMI-IXOXFDKPSA-N 0.000 description 4
- AIZVVCMAFRREQS-GUBZILKMSA-N Pro-Cys-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AIZVVCMAFRREQS-GUBZILKMSA-N 0.000 description 4
- OLTFZQIYCNOBLI-DCAQKATOSA-N Pro-Cys-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O OLTFZQIYCNOBLI-DCAQKATOSA-N 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- SQBLRDDJTUJDMV-ACZMJKKPSA-N Ser-Glu-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O SQBLRDDJTUJDMV-ACZMJKKPSA-N 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 108010041111 Thrombopoietin Proteins 0.000 description 4
- YYLHVUCSTXXKBS-IHRRRGAJSA-N Tyr-Pro-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O YYLHVUCSTXXKBS-IHRRRGAJSA-N 0.000 description 4
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 4
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 4
- KISFXYYRKKNLOP-IHRRRGAJSA-N Val-Phe-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)O)N KISFXYYRKKNLOP-IHRRRGAJSA-N 0.000 description 4
- ZLNYBMWGPOKSLW-LSJOCFKGSA-N Val-Val-Asp Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLNYBMWGPOKSLW-LSJOCFKGSA-N 0.000 description 4
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 239000012472 biological sample Substances 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000003599 detergent Substances 0.000 description 4
- 229920001249 ethyl cellulose Polymers 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 4
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 229940039781 leptin Drugs 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 239000006199 nebulizer Substances 0.000 description 4
- 210000000440 neutrophil Anatomy 0.000 description 4
- 230000006320 pegylation Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 108010094020 polyglycine Proteins 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 235000013930 proline Nutrition 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 229960004793 sucrose Drugs 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 125000001493 tyrosinyl group Chemical class [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
- 229960005356 urokinase Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 3
- MUSGYEMSJUFFHT-UWABRSFTSA-N 2-[(4R,7S,10S,13S,19S,22S,25S,28S,31S,34R)-34-[[(2S,3S)-2-[[(2R)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]-methylcarbamoyl]-25-(3-amino-3-oxopropyl)-7-(3-carbamimidamidopropyl)-10-(1H-imidazol-5-ylmethyl)-19-(1H-indol-3-ylmethyl)-13,17-dimethyl-28-[(1-methylindol-3-yl)methyl]-6,9,12,15,18,21,24,27,30,33-decaoxo-31-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29,32-decazacyclopentatriacont-22-yl]acetic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](N)Cc1ccc(O)cc1)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](C)NC(=O)CN(C)C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2cn(C)c3ccccc23)NC(=O)[C@@H](NC1=O)C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)C(N)=O MUSGYEMSJUFFHT-UWABRSFTSA-N 0.000 description 3
- QMOQBVOBWVNSNO-UHFFFAOYSA-N 2-[[2-[[2-[(2-azaniumylacetyl)amino]acetyl]amino]acetyl]amino]acetate Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(O)=O QMOQBVOBWVNSNO-UHFFFAOYSA-N 0.000 description 3
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 3
- SUHLZMHFRALVSY-YUMQZZPRSA-N Ala-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)NCC(O)=O SUHLZMHFRALVSY-YUMQZZPRSA-N 0.000 description 3
- 102100025683 Alkaline phosphatase, tissue-nonspecific isozyme Human genes 0.000 description 3
- OZNSCVPYWZRQPY-CIUDSAMLSA-N Arg-Asp-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O OZNSCVPYWZRQPY-CIUDSAMLSA-N 0.000 description 3
- PBSOQGZLPFVXPU-YUMQZZPRSA-N Arg-Glu-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O PBSOQGZLPFVXPU-YUMQZZPRSA-N 0.000 description 3
- QNNBHTFDFFFHGC-KKUMJFAQSA-N Asn-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QNNBHTFDFFFHGC-KKUMJFAQSA-N 0.000 description 3
- DONWIPDSZZJHHK-HJGDQZAQSA-N Asp-Lys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N)O DONWIPDSZZJHHK-HJGDQZAQSA-N 0.000 description 3
- QOJJMJKTMKNFEF-ZKWXMUAHSA-N Asp-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O QOJJMJKTMKNFEF-ZKWXMUAHSA-N 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 3
- 101100315624 Caenorhabditis elegans tyr-1 gene Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 108010087819 Fc receptors Proteins 0.000 description 3
- 102000009109 Fc receptors Human genes 0.000 description 3
- ZEEPYMXTJWIMSN-GUBZILKMSA-N Gln-Lys-Ser Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@@H](N)CCC(N)=O ZEEPYMXTJWIMSN-GUBZILKMSA-N 0.000 description 3
- UWMDGPFFTKDUIY-HJGDQZAQSA-N Gln-Pro-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O UWMDGPFFTKDUIY-HJGDQZAQSA-N 0.000 description 3
- SVZIKUHLRKVZIF-GUBZILKMSA-N Glu-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N SVZIKUHLRKVZIF-GUBZILKMSA-N 0.000 description 3
- CKOFNWCLWRYUHK-XHNCKOQMSA-N Glu-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N)C(=O)O CKOFNWCLWRYUHK-XHNCKOQMSA-N 0.000 description 3
- ZYRXTRTUCAVNBQ-GVXVVHGQSA-N Glu-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZYRXTRTUCAVNBQ-GVXVVHGQSA-N 0.000 description 3
- UFPXDFOYHVEIPI-BYPYZUCNSA-N Gly-Gly-Asp Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O UFPXDFOYHVEIPI-BYPYZUCNSA-N 0.000 description 3
- GJHWILMUOANXTG-WPRPVWTQSA-N Gly-Val-Arg Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GJHWILMUOANXTG-WPRPVWTQSA-N 0.000 description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- WOAMZMXCLBBQKW-KKUMJFAQSA-N His-Cys-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC2=CN=CN2)N)O WOAMZMXCLBBQKW-KKUMJFAQSA-N 0.000 description 3
- FYVHHKMHFPMBBG-GUBZILKMSA-N His-Gln-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N FYVHHKMHFPMBBG-GUBZILKMSA-N 0.000 description 3
- CSTDQOOBZBAJKE-BWAGICSOSA-N His-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC2=CN=CN2)N)O CSTDQOOBZBAJKE-BWAGICSOSA-N 0.000 description 3
- 101000574445 Homo sapiens Alkaline phosphatase, tissue-nonspecific isozyme Proteins 0.000 description 3
- 102000002265 Human Growth Hormone Human genes 0.000 description 3
- 108010000521 Human Growth Hormone Proteins 0.000 description 3
- 239000000854 Human Growth Hormone Substances 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 3
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000012741 Laemmli sample buffer Substances 0.000 description 3
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 3
- DAYQSYGBCUKVKT-VOAKCMCISA-N Leu-Thr-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O DAYQSYGBCUKVKT-VOAKCMCISA-N 0.000 description 3
- VUBIPAHVHMZHCM-KKUMJFAQSA-N Leu-Tyr-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CC=C(O)C=C1 VUBIPAHVHMZHCM-KKUMJFAQSA-N 0.000 description 3
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 3
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 3
- KCXUCYYZNZFGLL-SRVKXCTJSA-N Lys-Ala-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O KCXUCYYZNZFGLL-SRVKXCTJSA-N 0.000 description 3
- LUTDBHBIHHREDC-IHRRRGAJSA-N Lys-Pro-Lys Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(O)=O LUTDBHBIHHREDC-IHRRRGAJSA-N 0.000 description 3
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- YRYOXRMDHALAFL-UHFFFAOYSA-N N-(3-oxohexanoyl)homoserine lactone Chemical compound CCCC(=O)CC(=O)NC1CCOC1=O YRYOXRMDHALAFL-UHFFFAOYSA-N 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 102000015336 Nerve Growth Factor Human genes 0.000 description 3
- 102000004140 Oncostatin M Human genes 0.000 description 3
- 108090000630 Oncostatin M Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- JOXIIFVCSATTDH-IHPCNDPISA-N Phe-Asn-Trp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N JOXIIFVCSATTDH-IHPCNDPISA-N 0.000 description 3
- OMHMIXFFRPMYHB-SRVKXCTJSA-N Phe-Cys-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N OMHMIXFFRPMYHB-SRVKXCTJSA-N 0.000 description 3
- ZJPGOXWRFNKIQL-JYJNAYRXSA-N Phe-Pro-Pro Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=CC=C1 ZJPGOXWRFNKIQL-JYJNAYRXSA-N 0.000 description 3
- UAYHMOIGIQZLFR-NHCYSSNCSA-N Pro-Gln-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O UAYHMOIGIQZLFR-NHCYSSNCSA-N 0.000 description 3
- KIPIKSXPPLABPN-CIUDSAMLSA-N Pro-Glu-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1 KIPIKSXPPLABPN-CIUDSAMLSA-N 0.000 description 3
- FDMKYQQYJKYCLV-GUBZILKMSA-N Pro-Pro-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 FDMKYQQYJKYCLV-GUBZILKMSA-N 0.000 description 3
- GMJDSFYVTAMIBF-FXQIFTODSA-N Pro-Ser-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GMJDSFYVTAMIBF-FXQIFTODSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- RRVFEDGUXSYWOW-BZSNNMDCSA-N Ser-Phe-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RRVFEDGUXSYWOW-BZSNNMDCSA-N 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- BKVICMPZWRNWOC-RHYQMDGZSA-N Thr-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O BKVICMPZWRNWOC-RHYQMDGZSA-N 0.000 description 3
- 102000036693 Thrombopoietin Human genes 0.000 description 3
- BVDHHLMIZFCAAU-BZSNNMDCSA-N Tyr-Cys-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O BVDHHLMIZFCAAU-BZSNNMDCSA-N 0.000 description 3
- YWXMGBUGMLJMIP-IHPCNDPISA-N Tyr-Cys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC3=CC=C(C=C3)O)N YWXMGBUGMLJMIP-IHPCNDPISA-N 0.000 description 3
- PWKMJDQXKCENMF-MEYUZBJRSA-N Tyr-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O PWKMJDQXKCENMF-MEYUZBJRSA-N 0.000 description 3
- LVILBTSHPTWDGE-PMVMPFDFSA-N Tyr-Trp-Lys Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(O)=O)C1=CC=C(O)C=C1 LVILBTSHPTWDGE-PMVMPFDFSA-N 0.000 description 3
- SQUMHUZLJDUROQ-YDHLFZDLSA-N Tyr-Val-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O SQUMHUZLJDUROQ-YDHLFZDLSA-N 0.000 description 3
- KSFXWENSJABBFI-ZKWXMUAHSA-N Val-Ser-Asn Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KSFXWENSJABBFI-ZKWXMUAHSA-N 0.000 description 3
- KRAHMIJVUPUOTQ-DCAQKATOSA-N Val-Ser-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N KRAHMIJVUPUOTQ-DCAQKATOSA-N 0.000 description 3
- BZDGLJPROOOUOZ-XGEHTFHBSA-N Val-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N)O BZDGLJPROOOUOZ-XGEHTFHBSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 239000012062 aqueous buffer Substances 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 238000006664 bond formation reaction Methods 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 229940105329 carboxymethylcellulose Drugs 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 239000013613 expression plasmid Substances 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
- 101150089730 gly-10 gene Proteins 0.000 description 3
- 230000003394 haemopoietic effect Effects 0.000 description 3
- 238000005534 hematocrit Methods 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 229930027917 kanamycin Natural products 0.000 description 3
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 3
- 229960000318 kanamycin Drugs 0.000 description 3
- 229930182823 kanamycin A Natural products 0.000 description 3
- 229960001375 lactose Drugs 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 108010057821 leucylproline Proteins 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 108010003700 lysyl aspartic acid Proteins 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 239000013631 noncovalent dimer Substances 0.000 description 3
- MXHCPCSDRGLRER-UHFFFAOYSA-N pentaglycine Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(O)=O MXHCPCSDRGLRER-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 3
- 229920000232 polyglycine polymer Polymers 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 150000004804 polysaccharides Chemical class 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 239000003380 propellant Substances 0.000 description 3
- 230000009145 protein modification Effects 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- 108010005652 splenotritin Proteins 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical group O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 108010044292 tryptophyltyrosine Proteins 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 229920003169 water-soluble polymer Polymers 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 2
- JPOKAKNGULMYHZ-UILVTTEASA-N (2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-6-amino-2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-3-(4-hydroxyp Chemical compound C([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N)C1=CC=C(O)C=C1 JPOKAKNGULMYHZ-UILVTTEASA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- AUFACLFHBAGZEN-ZLUOBGJFSA-N Ala-Ser-Cys Chemical compound N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O AUFACLFHBAGZEN-ZLUOBGJFSA-N 0.000 description 2
- YJHKTAMKPGFJCT-NRPADANISA-N Ala-Val-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O YJHKTAMKPGFJCT-NRPADANISA-N 0.000 description 2
- QQJSJIBESHAJPM-IHRRRGAJSA-N Arg-Cys-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QQJSJIBESHAJPM-IHRRRGAJSA-N 0.000 description 2
- BGDILZXXDJCKPF-CIUDSAMLSA-N Arg-Gln-Cys Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(O)=O BGDILZXXDJCKPF-CIUDSAMLSA-N 0.000 description 2
- MZRBYBIQTIKERR-GUBZILKMSA-N Arg-Glu-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MZRBYBIQTIKERR-GUBZILKMSA-N 0.000 description 2
- SKTGPBFTMNLIHQ-KKUMJFAQSA-N Arg-Glu-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SKTGPBFTMNLIHQ-KKUMJFAQSA-N 0.000 description 2
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 2
- IRRMIGDCPOPZJW-ULQDDVLXSA-N Arg-His-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O IRRMIGDCPOPZJW-ULQDDVLXSA-N 0.000 description 2
- VVJTWSRNMJNDPN-IUCAKERBSA-N Arg-Met-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O VVJTWSRNMJNDPN-IUCAKERBSA-N 0.000 description 2
- ZUVMUOOHJYNJPP-XIRDDKMYSA-N Arg-Trp-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZUVMUOOHJYNJPP-XIRDDKMYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- NPDLYUOYAGBHFB-WDSKDSINSA-N Asn-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NPDLYUOYAGBHFB-WDSKDSINSA-N 0.000 description 2
- POTCZYQVVNXUIG-BQBZGAKWSA-N Asp-Gly-Pro Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O POTCZYQVVNXUIG-BQBZGAKWSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 2
- 229940121707 Calmodulin antagonist Drugs 0.000 description 2
- 101710132601 Capsid protein Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102100030851 Cortistatin Human genes 0.000 description 2
- 229930185483 Cortistatin Natural products 0.000 description 2
- DZLQXIFVQFTFJY-BYPYZUCNSA-N Cys-Gly-Gly Chemical compound SC[C@H](N)C(=O)NCC(=O)NCC(O)=O DZLQXIFVQFTFJY-BYPYZUCNSA-N 0.000 description 2
- XMVZMBGFIOQONW-GARJFASQSA-N Cys-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N)C(=O)O XMVZMBGFIOQONW-GARJFASQSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 2
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHNWZLGBTPUTQQ-QEJZJMRPSA-N Gln-Asp-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N DHNWZLGBTPUTQQ-QEJZJMRPSA-N 0.000 description 2
- LFIVHGMKWFGUGK-IHRRRGAJSA-N Gln-Glu-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N LFIVHGMKWFGUGK-IHRRRGAJSA-N 0.000 description 2
- NLKVNZUFDPWPNL-YUMQZZPRSA-N Glu-Arg-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O NLKVNZUFDPWPNL-YUMQZZPRSA-N 0.000 description 2
- FKJQNJCQTKUBCD-XPUUQOCRSA-N Gly-Ala-His Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O FKJQNJCQTKUBCD-XPUUQOCRSA-N 0.000 description 2
- MHHUEAIBJZWDBH-YUMQZZPRSA-N Gly-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CN MHHUEAIBJZWDBH-YUMQZZPRSA-N 0.000 description 2
- GYAUWXXORNTCHU-QWRGUYRKSA-N Gly-Cys-Tyr Chemical compound NCC(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 GYAUWXXORNTCHU-QWRGUYRKSA-N 0.000 description 2
- IDOGEHIWMJMAHT-BYPYZUCNSA-N Gly-Gly-Cys Chemical compound NCC(=O)NCC(=O)N[C@@H](CS)C(O)=O IDOGEHIWMJMAHT-BYPYZUCNSA-N 0.000 description 2
- HKSNHPVETYYJBK-LAEOZQHASA-N Gly-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)CN HKSNHPVETYYJBK-LAEOZQHASA-N 0.000 description 2
- QAMMIGULQSIRCD-IRXDYDNUSA-N Gly-Phe-Tyr Chemical compound C([C@H](NC(=O)C[NH3+])C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C([O-])=O)C1=CC=CC=C1 QAMMIGULQSIRCD-IRXDYDNUSA-N 0.000 description 2
- 108010015899 Glycopeptides Proteins 0.000 description 2
- 102000002068 Glycopeptides Human genes 0.000 description 2
- 102000018997 Growth Hormone Human genes 0.000 description 2
- 108010051696 Growth Hormone Proteins 0.000 description 2
- JHVCZQFWRLHUQR-DCAQKATOSA-N His-Arg-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N JHVCZQFWRLHUQR-DCAQKATOSA-N 0.000 description 2
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 2
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 2
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
- JHCVYQKVKOLAIU-NAKRPEOUSA-N Ile-Cys-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)O)N JHCVYQKVKOLAIU-NAKRPEOUSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102100026720 Interferon beta Human genes 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- 102100039880 Interleukin-1 receptor accessory protein Human genes 0.000 description 2
- 101710180389 Interleukin-1 receptor accessory protein Proteins 0.000 description 2
- 108090000177 Interleukin-11 Proteins 0.000 description 2
- 102000003815 Interleukin-11 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 102100039897 Interleukin-5 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- PIHFVNPEAHFNLN-KKUMJFAQSA-N Leu-Cys-Tyr Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N PIHFVNPEAHFNLN-KKUMJFAQSA-N 0.000 description 2
- CFZZDVMBRYFFNU-QWRGUYRKSA-N Leu-His-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)NCC(O)=O CFZZDVMBRYFFNU-QWRGUYRKSA-N 0.000 description 2
- JFSGIJSCJFQGSZ-MXAVVETBSA-N Leu-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC(C)C)N JFSGIJSCJFQGSZ-MXAVVETBSA-N 0.000 description 2
- IRMLZWSRWSGTOP-CIUDSAMLSA-N Leu-Ser-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O IRMLZWSRWSGTOP-CIUDSAMLSA-N 0.000 description 2
- VQXAVLQBQJMENB-SRVKXCTJSA-N Lys-Glu-Met Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O VQXAVLQBQJMENB-SRVKXCTJSA-N 0.000 description 2
- IEVXCWPVBYCJRZ-IXOXFDKPSA-N Lys-Thr-His Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 IEVXCWPVBYCJRZ-IXOXFDKPSA-N 0.000 description 2
- GMMLGMFBYCFCCX-KZVJFYERSA-N Met-Thr-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O GMMLGMFBYCFCCX-KZVJFYERSA-N 0.000 description 2
- XZFYRXDAULDNFX-UHFFFAOYSA-N N-L-cysteinyl-L-phenylalanine Natural products SCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XZFYRXDAULDNFX-UHFFFAOYSA-N 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 101710178358 Peptidoglycan-associated lipoprotein Proteins 0.000 description 2
- CQZNGNCAIXMAIQ-UBHSHLNASA-N Pro-Ala-Phe Chemical compound C[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O CQZNGNCAIXMAIQ-UBHSHLNASA-N 0.000 description 2
- KLSOMAFWRISSNI-OSUNSFLBSA-N Pro-Ile-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 KLSOMAFWRISSNI-OSUNSFLBSA-N 0.000 description 2
- FXGIMYRVJJEIIM-UWVGGRQHSA-N Pro-Leu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 FXGIMYRVJJEIIM-UWVGGRQHSA-N 0.000 description 2
- VTFXTWDFPTWNJY-RHYQMDGZSA-N Pro-Leu-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VTFXTWDFPTWNJY-RHYQMDGZSA-N 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N Pyridoxal Chemical compound CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
- 229940123578 Selectin antagonist Drugs 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- YUSRGTQIPCJNHQ-CIUDSAMLSA-N Ser-Arg-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O YUSRGTQIPCJNHQ-CIUDSAMLSA-N 0.000 description 2
- QGMLKFGTGXWAHF-IHRRRGAJSA-N Ser-Arg-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QGMLKFGTGXWAHF-IHRRRGAJSA-N 0.000 description 2
- UBRXAVQWXOWRSJ-ZLUOBGJFSA-N Ser-Asn-Asp Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CO)N)C(=O)N UBRXAVQWXOWRSJ-ZLUOBGJFSA-N 0.000 description 2
- CDVFZMOFNJPUDD-ACZMJKKPSA-N Ser-Gln-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CDVFZMOFNJPUDD-ACZMJKKPSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 102000005157 Somatostatin Human genes 0.000 description 2
- 108010056088 Somatostatin Proteins 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 101150006914 TRP1 gene Proteins 0.000 description 2
- NYTOUQBROMCLBJ-UHFFFAOYSA-N Tetranitromethane Chemical compound [O-][N+](=O)C([N+]([O-])=O)([N+]([O-])=O)[N+]([O-])=O NYTOUQBROMCLBJ-UHFFFAOYSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- OZUJUVFWMHTWCZ-HOCLYGCPSA-N Trp-Gly-His Chemical compound N[C@@H](Cc1c[nH]c2ccccc12)C(=O)NCC(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O OZUJUVFWMHTWCZ-HOCLYGCPSA-N 0.000 description 2
- UKWSFUSPGPBJGU-VFAJRCTISA-N Trp-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O UKWSFUSPGPBJGU-VFAJRCTISA-N 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102100024598 Tumor necrosis factor ligand superfamily member 10 Human genes 0.000 description 2
- 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 description 2
- KLGFILUOTCBNLJ-IHRRRGAJSA-N Tyr-Cys-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O KLGFILUOTCBNLJ-IHRRRGAJSA-N 0.000 description 2
- AVIQBBOOTZENLH-KKUMJFAQSA-N Tyr-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N AVIQBBOOTZENLH-KKUMJFAQSA-N 0.000 description 2
- YCMXFKWYJFZFKS-LAEOZQHASA-N Val-Gln-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N YCMXFKWYJFZFKS-LAEOZQHASA-N 0.000 description 2
- YTPLVNUZZOBFFC-SCZZXKLOSA-N Val-Gly-Pro Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N1CCC[C@@H]1C(O)=O YTPLVNUZZOBFFC-SCZZXKLOSA-N 0.000 description 2
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 2
- 102400000015 Vasoactive intestinal peptide Human genes 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 108010028939 alanyl-alanyl-lysyl-alanine Proteins 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000003466 anti-cipated effect Effects 0.000 description 2
- 230000001775 anti-pathogenic effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 108010068380 arginylarginine Proteins 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 108010005430 cortistatin Proteins 0.000 description 2
- DDRPLNQJNRBRNY-WYYADCIBSA-N cortistatin-14 Chemical compound C([C@H]1C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N1)NC(=O)[C@H]1NCCC1)C(=O)N[C@@H](CCCCN)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 DDRPLNQJNRBRNY-WYYADCIBSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229940014259 gelatin Drugs 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 108010000434 glycyl-alanyl-leucine Proteins 0.000 description 2
- 108010084264 glycyl-glycyl-cysteine Proteins 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000000122 growth hormone Substances 0.000 description 2
- 230000011132 hemopoiesis Effects 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 108010040030 histidinoalanine Proteins 0.000 description 2
- 108010028295 histidylhistidine Proteins 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 150000002463 imidates Chemical class 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 102000009634 interleukin-1 receptor antagonist activity proteins Human genes 0.000 description 2
- 108040001669 interleukin-1 receptor antagonist activity proteins Proteins 0.000 description 2
- 229940047122 interleukins Drugs 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 108010034529 leucyl-lysine Proteins 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000001906 matrix-assisted laser desorption--ionisation mass spectrometry Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 229940071648 metered dose inhaler Drugs 0.000 description 2
- 108010005942 methionylglycine Proteins 0.000 description 2
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 235000021313 oleic acid Nutrition 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- TVIDEEHSOPHZBR-AWEZNQCLSA-N para-(benzoyl)-phenylalanine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1C(=O)C1=CC=CC=C1 TVIDEEHSOPHZBR-AWEZNQCLSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 108010083476 phenylalanyltryptophan Proteins 0.000 description 2
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108700042769 prolyl-leucyl-glycine Proteins 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 2
- 108700042226 ras Genes Proteins 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000013878 renal filtration Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 239000002412 selectin antagonist Substances 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 2
- 229960000553 somatostatin Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 108010038745 tryptophylglycine Proteins 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 108010020532 tyrosyl-proline Proteins 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- FXYPGCIGRDZWNR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSCCC(=O)ON1C(=O)CCC1=O FXYPGCIGRDZWNR-UHFFFAOYSA-N 0.000 description 1
- IZUAHLHTQJCCLJ-UHFFFAOYSA-N (2-chloro-1,1,2,2-tetrafluoroethyl) hypochlorite Chemical compound FC(F)(Cl)C(F)(F)OCl IZUAHLHTQJCCLJ-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- NTUPOKHATNSWCY-PMPSAXMXSA-N (2s)-2-[[(2s)-1-[(2r)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=CC=C1 NTUPOKHATNSWCY-PMPSAXMXSA-N 0.000 description 1
- IESDGNYHXIOKRW-YXMSTPNBSA-N (2s)-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s,3r)-2-amino-3-hydroxybutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IESDGNYHXIOKRW-YXMSTPNBSA-N 0.000 description 1
- NYJVPTKMDYSZDU-MRNVWEPHSA-N (2s)-2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-1-[2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-3-carboxypropanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=CC=C1 NYJVPTKMDYSZDU-MRNVWEPHSA-N 0.000 description 1
- DIBLBAURNYJYBF-XLXZRNDBSA-N (2s)-2-[[(2s)-2-[[2-[[(2s)-6-amino-2-[[(2s)-2-amino-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 DIBLBAURNYJYBF-XLXZRNDBSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 1
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 1
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- XLBBKEHLEPNMMF-SSUNCQRMSA-N 129038-42-2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)[C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(O)=O)C1=CC=CC=C1 XLBBKEHLEPNMMF-SSUNCQRMSA-N 0.000 description 1
- 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 1
- OHMHBGPWCHTMQE-UHFFFAOYSA-N 2,2-dichloro-1,1,1-trifluoroethane Chemical compound FC(F)(F)C(Cl)Cl OHMHBGPWCHTMQE-UHFFFAOYSA-N 0.000 description 1
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- JEPVUMTVFPQKQE-AAKCMJRZSA-N 2-[(1s,2s,3r,4s)-1,2,3,4,5-pentahydroxypentyl]-1,3-thiazolidine-4-carboxylic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C1NC(C(O)=O)CS1 JEPVUMTVFPQKQE-AAKCMJRZSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- JQPFYXFVUKHERX-UHFFFAOYSA-N 2-hydroxy-2-cyclohexen-1-one Natural products OC1=CCCCC1=O JQPFYXFVUKHERX-UHFFFAOYSA-N 0.000 description 1
- 125000003816 2-hydroxybenzoyl group Chemical group OC1=C(C(=O)*)C=CC=C1 0.000 description 1
- VJINKBZUJYGZGP-UHFFFAOYSA-N 3-(1-aminopropylideneamino)propyl-trimethylazanium Chemical compound CCC(N)=NCCC[N+](C)(C)C VJINKBZUJYGZGP-UHFFFAOYSA-N 0.000 description 1
- BIGBDMFRWJRLGJ-UHFFFAOYSA-N 3-benzyl-1,5-didiazoniopenta-1,4-diene-2,4-diolate Chemical compound [N-]=[N+]=CC(=O)C(C(=O)C=[N+]=[N-])CC1=CC=CC=C1 BIGBDMFRWJRLGJ-UHFFFAOYSA-N 0.000 description 1
- CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- NLPWSMKACWGINL-UHFFFAOYSA-N 4-azido-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(N=[N+]=[N-])C=C1O NLPWSMKACWGINL-UHFFFAOYSA-N 0.000 description 1
- ZMYKITJYWFYRFJ-UHFFFAOYSA-N 4-oxo-4-(2-phenylethylamino)butanoic acid Chemical compound OC(=O)CCC(=O)NCCC1=CC=CC=C1 ZMYKITJYWFYRFJ-UHFFFAOYSA-N 0.000 description 1
- 102100033051 40S ribosomal protein S19 Human genes 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 102400001318 Adrenomedullin Human genes 0.000 description 1
- 101800004616 Adrenomedullin Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- SITWEMZOJNKJCH-WDSKDSINSA-N Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N SITWEMZOJNKJCH-WDSKDSINSA-N 0.000 description 1
- SVBXIUDNTRTKHE-CIUDSAMLSA-N Ala-Arg-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O SVBXIUDNTRTKHE-CIUDSAMLSA-N 0.000 description 1
- YWWATNIVMOCSAV-UBHSHLNASA-N Ala-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YWWATNIVMOCSAV-UBHSHLNASA-N 0.000 description 1
- KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 1
- KUDREHRZRIVKHS-UWJYBYFXSA-N Ala-Asp-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KUDREHRZRIVKHS-UWJYBYFXSA-N 0.000 description 1
- NWVVKQZOVSTDBQ-CIUDSAMLSA-N Ala-Glu-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NWVVKQZOVSTDBQ-CIUDSAMLSA-N 0.000 description 1
- FBHOPGDGELNWRH-DRZSPHRISA-N Ala-Glu-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O FBHOPGDGELNWRH-DRZSPHRISA-N 0.000 description 1
- SIGTYDNEPYEXGK-ZANVPECISA-N Ala-Gly-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)CNC(=O)[C@@H](N)C)C(O)=O)=CNC2=C1 SIGTYDNEPYEXGK-ZANVPECISA-N 0.000 description 1
- SMCGQGDVTPFXKB-XPUUQOCRSA-N Ala-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N SMCGQGDVTPFXKB-XPUUQOCRSA-N 0.000 description 1
- CKLDHDOIYBVUNP-KBIXCLLPSA-N Ala-Ile-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O CKLDHDOIYBVUNP-KBIXCLLPSA-N 0.000 description 1
- OYJCVIGKMXUVKB-GARJFASQSA-N Ala-Leu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N OYJCVIGKMXUVKB-GARJFASQSA-N 0.000 description 1
- QUIGLPSHIFPEOV-CIUDSAMLSA-N Ala-Lys-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O QUIGLPSHIFPEOV-CIUDSAMLSA-N 0.000 description 1
- CYBJZLQSUJEMAS-LFSVMHDDSA-N Ala-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)N)O CYBJZLQSUJEMAS-LFSVMHDDSA-N 0.000 description 1
- IORKCNUBHNIMKY-CIUDSAMLSA-N Ala-Pro-Glu Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O IORKCNUBHNIMKY-CIUDSAMLSA-N 0.000 description 1
- FFZJHQODAYHGPO-KZVJFYERSA-N Ala-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N FFZJHQODAYHGPO-KZVJFYERSA-N 0.000 description 1
- IPWKGIFRRBGCJO-IMJSIDKUSA-N Ala-Ser Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](CO)C([O-])=O IPWKGIFRRBGCJO-IMJSIDKUSA-N 0.000 description 1
- JJHBEVZAZXZREW-LFSVMHDDSA-N Ala-Thr-Phe Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](Cc1ccccc1)C(O)=O JJHBEVZAZXZREW-LFSVMHDDSA-N 0.000 description 1
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- WVRUNFYJIHNFKD-WDSKDSINSA-N Arg-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N WVRUNFYJIHNFKD-WDSKDSINSA-N 0.000 description 1
- OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 description 1
- UXJCMQFPDWCHKX-DCAQKATOSA-N Arg-Arg-Glu Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O UXJCMQFPDWCHKX-DCAQKATOSA-N 0.000 description 1
- SIFXMYAHXJGAFC-WDSKDSINSA-N Arg-Asp Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O SIFXMYAHXJGAFC-WDSKDSINSA-N 0.000 description 1
- YSUVMPICYVWRBX-VEVYYDQMSA-N Arg-Asp-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O YSUVMPICYVWRBX-VEVYYDQMSA-N 0.000 description 1
- OSASDIVHOSJVII-WDSKDSINSA-N Arg-Cys Chemical compound SC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N OSASDIVHOSJVII-WDSKDSINSA-N 0.000 description 1
- PMGDADKJMCOXHX-BQBZGAKWSA-N Arg-Gln Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(O)=O PMGDADKJMCOXHX-BQBZGAKWSA-N 0.000 description 1
- HPKSHFSEXICTLI-CIUDSAMLSA-N Arg-Glu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HPKSHFSEXICTLI-CIUDSAMLSA-N 0.000 description 1
- QAODJPUKWNNNRP-DCAQKATOSA-N Arg-Glu-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QAODJPUKWNNNRP-DCAQKATOSA-N 0.000 description 1
- RKRSYHCNPFGMTA-CIUDSAMLSA-N Arg-Glu-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O RKRSYHCNPFGMTA-CIUDSAMLSA-N 0.000 description 1
- XLWSGICNBZGYTA-CIUDSAMLSA-N Arg-Glu-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XLWSGICNBZGYTA-CIUDSAMLSA-N 0.000 description 1
- NYZGVTGOMPHSJW-CIUDSAMLSA-N Arg-Glu-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)CN=C(N)N NYZGVTGOMPHSJW-CIUDSAMLSA-N 0.000 description 1
- PNQWAUXQDBIJDY-GUBZILKMSA-N Arg-Glu-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNQWAUXQDBIJDY-GUBZILKMSA-N 0.000 description 1
- QAXCZGMLVICQKS-SRVKXCTJSA-N Arg-Glu-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N QAXCZGMLVICQKS-SRVKXCTJSA-N 0.000 description 1
- OHYQKYUTLIPFOX-ZPFDUUQYSA-N Arg-Glu-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OHYQKYUTLIPFOX-ZPFDUUQYSA-N 0.000 description 1
- NKBQZKVMKJJDLX-SRVKXCTJSA-N Arg-Glu-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NKBQZKVMKJJDLX-SRVKXCTJSA-N 0.000 description 1
- OGUPCHKBOKJFMA-SRVKXCTJSA-N Arg-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N OGUPCHKBOKJFMA-SRVKXCTJSA-N 0.000 description 1
- DJAIOAKQIOGULM-DCAQKATOSA-N Arg-Glu-Met Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O DJAIOAKQIOGULM-DCAQKATOSA-N 0.000 description 1
- HPSVTWMFWCHKFN-GARJFASQSA-N Arg-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O HPSVTWMFWCHKFN-GARJFASQSA-N 0.000 description 1
- UFBURHXMKFQVLM-CIUDSAMLSA-N Arg-Glu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O UFBURHXMKFQVLM-CIUDSAMLSA-N 0.000 description 1
- NXDXECQFKHXHAM-HJGDQZAQSA-N Arg-Glu-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NXDXECQFKHXHAM-HJGDQZAQSA-N 0.000 description 1
- JAYIQMNQDMOBFY-KKUMJFAQSA-N Arg-Glu-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JAYIQMNQDMOBFY-KKUMJFAQSA-N 0.000 description 1
- GOWZVQXTHUCNSQ-NHCYSSNCSA-N Arg-Glu-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O GOWZVQXTHUCNSQ-NHCYSSNCSA-N 0.000 description 1
- XUUXCWCKKCZEAW-YFKPBYRVSA-N Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N XUUXCWCKKCZEAW-YFKPBYRVSA-N 0.000 description 1
- BNODVYXZAAXSHW-IUCAKERBSA-N Arg-His Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 BNODVYXZAAXSHW-IUCAKERBSA-N 0.000 description 1
- QYLJIYOGHRGUIH-CIUDSAMLSA-N Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N QYLJIYOGHRGUIH-CIUDSAMLSA-N 0.000 description 1
- WYBVBIHNJWOLCJ-IUCAKERBSA-N Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N WYBVBIHNJWOLCJ-IUCAKERBSA-N 0.000 description 1
- YBZMTKUDWXZLIX-UWVGGRQHSA-N Arg-Leu-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YBZMTKUDWXZLIX-UWVGGRQHSA-N 0.000 description 1
- JQFZHHSQMKZLRU-IUCAKERBSA-N Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N JQFZHHSQMKZLRU-IUCAKERBSA-N 0.000 description 1
- ROWCTNFEMKOIFQ-YUMQZZPRSA-N Arg-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N ROWCTNFEMKOIFQ-YUMQZZPRSA-N 0.000 description 1
- NYDIVDKTULRINZ-AVGNSLFASA-N Arg-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N NYDIVDKTULRINZ-AVGNSLFASA-N 0.000 description 1
- PQBHGSGQZSOLIR-RYUDHWBXSA-N Arg-Phe Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PQBHGSGQZSOLIR-RYUDHWBXSA-N 0.000 description 1
- GSUFZRURORXYTM-STQMWFEESA-N Arg-Phe-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 GSUFZRURORXYTM-STQMWFEESA-N 0.000 description 1
- SLQQPJBDBVPVQV-JYJNAYRXSA-N Arg-Phe-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O SLQQPJBDBVPVQV-JYJNAYRXSA-N 0.000 description 1
- LQJAALCCPOTJGB-YUMQZZPRSA-N Arg-Pro Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O LQJAALCCPOTJGB-YUMQZZPRSA-N 0.000 description 1
- IJYZHIOOBGIINM-WDSKDSINSA-N Arg-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N IJYZHIOOBGIINM-WDSKDSINSA-N 0.000 description 1
- XNSKSTRGQIPTSE-ACZMJKKPSA-N Arg-Thr Chemical compound C[C@@H]([C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O XNSKSTRGQIPTSE-ACZMJKKPSA-N 0.000 description 1
- QADCERNTBWTXFV-JSGCOSHPSA-N Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCNC(N)=N)N)C(O)=O)=CNC2=C1 QADCERNTBWTXFV-JSGCOSHPSA-N 0.000 description 1
- XTWSWDJMIKUJDQ-RYUDHWBXSA-N Arg-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XTWSWDJMIKUJDQ-RYUDHWBXSA-N 0.000 description 1
- UVTGNSWSRSCPLP-UHFFFAOYSA-N Arg-Tyr Natural products NC(CCNC(=N)N)C(=O)NC(Cc1ccc(O)cc1)C(=O)O UVTGNSWSRSCPLP-UHFFFAOYSA-N 0.000 description 1
- DAQIJMOLTMGJLO-YUMQZZPRSA-N Arg-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N DAQIJMOLTMGJLO-YUMQZZPRSA-N 0.000 description 1
- YJRORCOAFUZVKA-FXQIFTODSA-N Asn-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N)CN=C(N)N YJRORCOAFUZVKA-FXQIFTODSA-N 0.000 description 1
- BDMIFVIWCNLDCT-CIUDSAMLSA-N Asn-Arg-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O BDMIFVIWCNLDCT-CIUDSAMLSA-N 0.000 description 1
- VJTWLBMESLDOMK-WDSKDSINSA-N Asn-Gln-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O VJTWLBMESLDOMK-WDSKDSINSA-N 0.000 description 1
- PPMTUXJSQDNUDE-CIUDSAMLSA-N Asn-Glu-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PPMTUXJSQDNUDE-CIUDSAMLSA-N 0.000 description 1
- WONGRTVAMHFGBE-WDSKDSINSA-N Asn-Gly-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N WONGRTVAMHFGBE-WDSKDSINSA-N 0.000 description 1
- LGCVSPFCFXWUEY-IHPCNDPISA-N Asn-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N LGCVSPFCFXWUEY-IHPCNDPISA-N 0.000 description 1
- PSZNHSNIGMJYOZ-WDSKDSINSA-N Asp-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PSZNHSNIGMJYOZ-WDSKDSINSA-N 0.000 description 1
- WSOKZUVWBXVJHX-CIUDSAMLSA-N Asp-Arg-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O WSOKZUVWBXVJHX-CIUDSAMLSA-N 0.000 description 1
- ZSJFGGSPCCHMNE-LAEOZQHASA-N Asp-Gln-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)N ZSJFGGSPCCHMNE-LAEOZQHASA-N 0.000 description 1
- IJHUZMGJRGNXIW-CIUDSAMLSA-N Asp-Glu-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IJHUZMGJRGNXIW-CIUDSAMLSA-N 0.000 description 1
- PDECQIHABNQRHN-GUBZILKMSA-N Asp-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(O)=O PDECQIHABNQRHN-GUBZILKMSA-N 0.000 description 1
- SNDBKTFJWVEVPO-WHFBIAKZSA-N Asp-Gly-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SNDBKTFJWVEVPO-WHFBIAKZSA-N 0.000 description 1
- WNGZKSVJFDZICU-XIRDDKMYSA-N Asp-Leu-Trp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(=O)O)N WNGZKSVJFDZICU-XIRDDKMYSA-N 0.000 description 1
- DPNWSMBUYCLEDG-CIUDSAMLSA-N Asp-Lys-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O DPNWSMBUYCLEDG-CIUDSAMLSA-N 0.000 description 1
- HTSSXFASOUSJQG-IHPCNDPISA-N Asp-Tyr-Trp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O HTSSXFASOUSJQG-IHPCNDPISA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000033932 Blackfan-Diamond anemia Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108050005711 C Chemokine Proteins 0.000 description 1
- 102000017483 C chemokine Human genes 0.000 description 1
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 1
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 108700012434 CCL3 Proteins 0.000 description 1
- 229940123494 CD20 antagonist Drugs 0.000 description 1
- 102100027207 CD27 antigen Human genes 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 229940123189 CD40 agonist Drugs 0.000 description 1
- 229940122551 CD40 antagonist Drugs 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 108010051834 CTTHWGFTLC peptide Proteins 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 108010083698 Chemokine CCL26 Proteins 0.000 description 1
- 102000000013 Chemokine CCL3 Human genes 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 108010014419 Chemokine CXCL1 Proteins 0.000 description 1
- 102000016950 Chemokine CXCL1 Human genes 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 1
- 208000028702 Congenital thrombocyte disease Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- QFMCHXSGIZPBKG-ZLUOBGJFSA-N Cys-Ala-Asp Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N QFMCHXSGIZPBKG-ZLUOBGJFSA-N 0.000 description 1
- RRIJEABIXPKSGP-FXQIFTODSA-N Cys-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CS RRIJEABIXPKSGP-FXQIFTODSA-N 0.000 description 1
- RGTVXXNMOGHRAY-WDSKDSINSA-N Cys-Arg Chemical compound SC[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RGTVXXNMOGHRAY-WDSKDSINSA-N 0.000 description 1
- SZQCDCKIGWQAQN-FXQIFTODSA-N Cys-Arg-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O SZQCDCKIGWQAQN-FXQIFTODSA-N 0.000 description 1
- CLDCTNHPILWQCW-CIUDSAMLSA-N Cys-Arg-Glu Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N CLDCTNHPILWQCW-CIUDSAMLSA-N 0.000 description 1
- SFRQEQGPRTVDPO-NRPADANISA-N Cys-Gln-Val Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O SFRQEQGPRTVDPO-NRPADANISA-N 0.000 description 1
- FIADUEYFRSCCIK-CIUDSAMLSA-N Cys-Glu-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FIADUEYFRSCCIK-CIUDSAMLSA-N 0.000 description 1
- DZIGZIIJIGGANI-FXQIFTODSA-N Cys-Glu-Gln Chemical compound SC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O DZIGZIIJIGGANI-FXQIFTODSA-N 0.000 description 1
- KABHAOSDMIYXTR-GUBZILKMSA-N Cys-Glu-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CS)N KABHAOSDMIYXTR-GUBZILKMSA-N 0.000 description 1
- OXOQBEVULIBOSH-ZDLURKLDSA-N Cys-Gly-Thr Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O OXOQBEVULIBOSH-ZDLURKLDSA-N 0.000 description 1
- XZKJEOMFLDVXJG-KATARQTJSA-N Cys-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)N)O XZKJEOMFLDVXJG-KATARQTJSA-N 0.000 description 1
- ZXCAQANTQWBICD-DCAQKATOSA-N Cys-Lys-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N ZXCAQANTQWBICD-DCAQKATOSA-N 0.000 description 1
- NXQCSPVUPLUTJH-WHFBIAKZSA-N Cys-Ser-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O NXQCSPVUPLUTJH-WHFBIAKZSA-N 0.000 description 1
- GGRDJANMZPGMNS-CIUDSAMLSA-N Cys-Ser-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O GGRDJANMZPGMNS-CIUDSAMLSA-N 0.000 description 1
- YWEHYKGJWHPGPY-XGEHTFHBSA-N Cys-Thr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N)O YWEHYKGJWHPGPY-XGEHTFHBSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 101000802895 Dendroaspis angusticeps Fasciculin-1 Proteins 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 201000004449 Diamond-Blackfan anemia Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 102100032257 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102400000686 Endothelin-1 Human genes 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 208000026019 Fanconi renotubular syndrome Diseases 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 206010016880 Folate deficiency Diseases 0.000 description 1
- 208000010188 Folic Acid Deficiency Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102400001301 Gasdermin-B, C-terminal Human genes 0.000 description 1
- OPINTGHFESTVAX-BQBZGAKWSA-N Gln-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N OPINTGHFESTVAX-BQBZGAKWSA-N 0.000 description 1
- LZRMPXRYLLTAJX-GUBZILKMSA-N Gln-Arg-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O LZRMPXRYLLTAJX-GUBZILKMSA-N 0.000 description 1
- PZVJDMJHKUWSIV-AVGNSLFASA-N Gln-Cys-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)N)N)O PZVJDMJHKUWSIV-AVGNSLFASA-N 0.000 description 1
- LVNILKSSFHCSJZ-IHRRRGAJSA-N Gln-Gln-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N LVNILKSSFHCSJZ-IHRRRGAJSA-N 0.000 description 1
- BLOXULLYFRGYKZ-GUBZILKMSA-N Gln-Glu-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O BLOXULLYFRGYKZ-GUBZILKMSA-N 0.000 description 1
- OTQSTOXRUBVWAP-NRPADANISA-N Gln-Ser-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O OTQSTOXRUBVWAP-NRPADANISA-N 0.000 description 1
- CSMHMEATMDCQNY-DZKIICNBSA-N Gln-Val-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CSMHMEATMDCQNY-DZKIICNBSA-N 0.000 description 1
- MPZWMIIOPAPAKE-BQBZGAKWSA-N Glu-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N MPZWMIIOPAPAKE-BQBZGAKWSA-N 0.000 description 1
- AVZHGSCDKIQZPQ-CIUDSAMLSA-N Glu-Arg-Ala Chemical compound C[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CCC(O)=O)C(O)=O AVZHGSCDKIQZPQ-CIUDSAMLSA-N 0.000 description 1
- WOMUDRVDJMHTCV-DCAQKATOSA-N Glu-Arg-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WOMUDRVDJMHTCV-DCAQKATOSA-N 0.000 description 1
- CVPXINNKRTZBMO-CIUDSAMLSA-N Glu-Arg-Asn Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)CN=C(N)N CVPXINNKRTZBMO-CIUDSAMLSA-N 0.000 description 1
- DIXKFOPPGWKZLY-CIUDSAMLSA-N Glu-Arg-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O DIXKFOPPGWKZLY-CIUDSAMLSA-N 0.000 description 1
- IYAUFWMUCGBFMQ-CIUDSAMLSA-N Glu-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)CN=C(N)N IYAUFWMUCGBFMQ-CIUDSAMLSA-N 0.000 description 1
- RCCDHXSRMWCOOY-GUBZILKMSA-N Glu-Arg-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O RCCDHXSRMWCOOY-GUBZILKMSA-N 0.000 description 1
- CGYDXNKRIMJMLV-GUBZILKMSA-N Glu-Arg-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O CGYDXNKRIMJMLV-GUBZILKMSA-N 0.000 description 1
- PBEQPAZRHDVJQI-SRVKXCTJSA-N Glu-Arg-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N PBEQPAZRHDVJQI-SRVKXCTJSA-N 0.000 description 1
- VTTSANCGJWLPNC-ZPFDUUQYSA-N Glu-Arg-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VTTSANCGJWLPNC-ZPFDUUQYSA-N 0.000 description 1
- KKCUFHUTMKQQCF-SRVKXCTJSA-N Glu-Arg-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O KKCUFHUTMKQQCF-SRVKXCTJSA-N 0.000 description 1
- OJGLIOXAKGFFDW-SRVKXCTJSA-N Glu-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N OJGLIOXAKGFFDW-SRVKXCTJSA-N 0.000 description 1
- KEBACWCLVOXFNC-DCAQKATOSA-N Glu-Arg-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(O)=O KEBACWCLVOXFNC-DCAQKATOSA-N 0.000 description 1
- LTUVYLVIZHJCOQ-KKUMJFAQSA-N Glu-Arg-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LTUVYLVIZHJCOQ-KKUMJFAQSA-N 0.000 description 1
- VPKBCVUDBNINAH-GARJFASQSA-N Glu-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N)C(=O)O VPKBCVUDBNINAH-GARJFASQSA-N 0.000 description 1
- WOSRKEJQESVHGA-CIUDSAMLSA-N Glu-Arg-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O WOSRKEJQESVHGA-CIUDSAMLSA-N 0.000 description 1
- SRZLHYPAOXBBSB-HJGDQZAQSA-N Glu-Arg-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SRZLHYPAOXBBSB-HJGDQZAQSA-N 0.000 description 1
- SYDJILXOZNEEDK-XIRDDKMYSA-N Glu-Arg-Trp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O SYDJILXOZNEEDK-XIRDDKMYSA-N 0.000 description 1
- GCYFUZJHAXJKKE-KKUMJFAQSA-N Glu-Arg-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GCYFUZJHAXJKKE-KKUMJFAQSA-N 0.000 description 1
- DYFJZDDQPNIPAB-NHCYSSNCSA-N Glu-Arg-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O DYFJZDDQPNIPAB-NHCYSSNCSA-N 0.000 description 1
- GLWXKFRTOHKGIT-ACZMJKKPSA-N Glu-Asn-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O GLWXKFRTOHKGIT-ACZMJKKPSA-N 0.000 description 1
- ILGFBUGLBSAQQB-GUBZILKMSA-N Glu-Glu-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ILGFBUGLBSAQQB-GUBZILKMSA-N 0.000 description 1
- PXXGVUVQWQGGIG-YUMQZZPRSA-N Glu-Gly-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N PXXGVUVQWQGGIG-YUMQZZPRSA-N 0.000 description 1
- CQAHWYDHKUWYIX-YUMQZZPRSA-N Glu-Pro-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O CQAHWYDHKUWYIX-YUMQZZPRSA-N 0.000 description 1
- DMYACXMQUABZIQ-NRPADANISA-N Glu-Ser-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O DMYACXMQUABZIQ-NRPADANISA-N 0.000 description 1
- DLISPGXMKZTWQG-IFFSRLJSSA-N Glu-Thr-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O DLISPGXMKZTWQG-IFFSRLJSSA-N 0.000 description 1
- YOTHMZZSJKKEHZ-SZMVWBNQSA-N Glu-Trp-Lys Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CCC(O)=O)=CNC2=C1 YOTHMZZSJKKEHZ-SZMVWBNQSA-N 0.000 description 1
- FGGKGJHCVMYGCD-UKJIMTQDSA-N Glu-Val-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FGGKGJHCVMYGCD-UKJIMTQDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- JLXVRFDTDUGQEE-YFKPBYRVSA-N Gly-Arg Chemical compound NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N JLXVRFDTDUGQEE-YFKPBYRVSA-N 0.000 description 1
- PYUCNHJQQVSPGN-BQBZGAKWSA-N Gly-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN)CN=C(N)N PYUCNHJQQVSPGN-BQBZGAKWSA-N 0.000 description 1
- OGCIHJPYKVSMTE-YUMQZZPRSA-N Gly-Arg-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O OGCIHJPYKVSMTE-YUMQZZPRSA-N 0.000 description 1
- UXJHNZODTMHWRD-WHFBIAKZSA-N Gly-Asn-Ala Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O UXJHNZODTMHWRD-WHFBIAKZSA-N 0.000 description 1
- GGEJHJIXRBTJPD-BYPYZUCNSA-N Gly-Asn-Gly Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O GGEJHJIXRBTJPD-BYPYZUCNSA-N 0.000 description 1
- GRIRDMVMJJDZKV-RCOVLWMOSA-N Gly-Asn-Val Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O GRIRDMVMJJDZKV-RCOVLWMOSA-N 0.000 description 1
- CEXINUGNTZFNRY-BYPYZUCNSA-N Gly-Cys-Gly Chemical compound [NH3+]CC(=O)N[C@@H](CS)C(=O)NCC([O-])=O CEXINUGNTZFNRY-BYPYZUCNSA-N 0.000 description 1
- PABFFPWEJMEVEC-JGVFFNPUSA-N Gly-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)CN)C(=O)O PABFFPWEJMEVEC-JGVFFNPUSA-N 0.000 description 1
- QPDUVFSVVAOUHE-XVKPBYJWSA-N Gly-Gln-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)CN)C(O)=O QPDUVFSVVAOUHE-XVKPBYJWSA-N 0.000 description 1
- DHDOADIPGZTAHT-YUMQZZPRSA-N Gly-Glu-Arg Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DHDOADIPGZTAHT-YUMQZZPRSA-N 0.000 description 1
- FIQQRCFQXGLOSZ-WDSKDSINSA-N Gly-Glu-Asp Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FIQQRCFQXGLOSZ-WDSKDSINSA-N 0.000 description 1
- HQRHFUYMGCHHJS-LURJTMIESA-N Gly-Gly-Arg Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N HQRHFUYMGCHHJS-LURJTMIESA-N 0.000 description 1
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 1
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 1
- INLIXXRWNUKVCF-JTQLQIEISA-N Gly-Gly-Tyr Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 INLIXXRWNUKVCF-JTQLQIEISA-N 0.000 description 1
- OLPPXYMMIARYAL-QMMMGPOBSA-N Gly-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)CN OLPPXYMMIARYAL-QMMMGPOBSA-N 0.000 description 1
- CQIIXEHDSZUSAG-QWRGUYRKSA-N Gly-His-His Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 CQIIXEHDSZUSAG-QWRGUYRKSA-N 0.000 description 1
- IUZGUFAJDBHQQV-YUMQZZPRSA-N Gly-Leu-Asn Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O IUZGUFAJDBHQQV-YUMQZZPRSA-N 0.000 description 1
- YIFUFYZELCMPJP-YUMQZZPRSA-N Gly-Leu-Cys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(O)=O YIFUFYZELCMPJP-YUMQZZPRSA-N 0.000 description 1
- QVDGHDFFYHKJPN-QWRGUYRKSA-N Gly-Phe-Cys Chemical compound NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CS)C(O)=O QVDGHDFFYHKJPN-QWRGUYRKSA-N 0.000 description 1
- VDCRBJACQKOSMS-JSGCOSHPSA-N Gly-Phe-Val Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O VDCRBJACQKOSMS-JSGCOSHPSA-N 0.000 description 1
- IXHQLZIWBCQBLQ-STQMWFEESA-N Gly-Pro-Phe Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IXHQLZIWBCQBLQ-STQMWFEESA-N 0.000 description 1
- CSMYMGFCEJWALV-WDSKDSINSA-N Gly-Ser-Gln Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O CSMYMGFCEJWALV-WDSKDSINSA-N 0.000 description 1
- YXTFLTJYLIAZQG-FJXKBIBVSA-N Gly-Thr-Arg Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YXTFLTJYLIAZQG-FJXKBIBVSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- DZMVESFTHXSSPZ-XVYDVKMFSA-N His-Ala-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DZMVESFTHXSSPZ-XVYDVKMFSA-N 0.000 description 1
- NIKBMHGRNAPJFW-IUCAKERBSA-N His-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 NIKBMHGRNAPJFW-IUCAKERBSA-N 0.000 description 1
- YPLYIXGKCRQZGW-SRVKXCTJSA-N His-Arg-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O YPLYIXGKCRQZGW-SRVKXCTJSA-N 0.000 description 1
- WMKXFMUJRCEGRP-SRVKXCTJSA-N His-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N WMKXFMUJRCEGRP-SRVKXCTJSA-N 0.000 description 1
- IMCHNUANCIGUKS-SRVKXCTJSA-N His-Glu-Arg Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IMCHNUANCIGUKS-SRVKXCTJSA-N 0.000 description 1
- STWGDDDFLUFCCA-GVXVVHGQSA-N His-Glu-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O STWGDDDFLUFCCA-GVXVVHGQSA-N 0.000 description 1
- PYNUBZSXKQKAHL-UWVGGRQHSA-N His-Gly-Arg Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O PYNUBZSXKQKAHL-UWVGGRQHSA-N 0.000 description 1
- FDQYIRHBVVUTJF-ZETCQYMHSA-N His-Gly-Gly Chemical compound [O-]C(=O)CNC(=O)CNC(=O)[C@@H]([NH3+])CC1=CN=CN1 FDQYIRHBVVUTJF-ZETCQYMHSA-N 0.000 description 1
- BSVLMPMIXPQNKC-KBPBESRZSA-N His-Phe-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O BSVLMPMIXPQNKC-KBPBESRZSA-N 0.000 description 1
- KRBMQYPTDYSENE-BQBZGAKWSA-N His-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CNC=N1 KRBMQYPTDYSENE-BQBZGAKWSA-N 0.000 description 1
- KECFCPNPPYCGBL-PMVMPFDFSA-N His-Trp-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CC4=CN=CN4)N KECFCPNPPYCGBL-PMVMPFDFSA-N 0.000 description 1
- MUENHEQLLUDKSC-PMVMPFDFSA-N His-Tyr-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CNC=N1 MUENHEQLLUDKSC-PMVMPFDFSA-N 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 1
- 101000852870 Homo sapiens Interferon alpha/beta receptor 1 Proteins 0.000 description 1
- 101001001420 Homo sapiens Interferon gamma receptor 1 Proteins 0.000 description 1
- 101001129187 Homo sapiens Patatin-like phospholipase domain-containing protein 2 Proteins 0.000 description 1
- 101001123069 Homo sapiens Protein phosphatase 1 regulatory subunit 42 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101100369992 Homo sapiens TNFSF10 gene Proteins 0.000 description 1
- 101100207070 Homo sapiens TNFSF8 gene Proteins 0.000 description 1
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 1
- 101000799466 Homo sapiens Thrombopoietin receptor Proteins 0.000 description 1
- 101000694103 Homo sapiens Thyroid peroxidase Proteins 0.000 description 1
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- YKRYHWJRQUSTKG-KBIXCLLPSA-N Ile-Ala-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YKRYHWJRQUSTKG-KBIXCLLPSA-N 0.000 description 1
- HYXQKVOADYPQEA-CIUDSAMLSA-N Ile-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N HYXQKVOADYPQEA-CIUDSAMLSA-N 0.000 description 1
- FVEWRQXNISSYFO-ZPFDUUQYSA-N Ile-Arg-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N FVEWRQXNISSYFO-ZPFDUUQYSA-N 0.000 description 1
- UMYZBHKAVTXWIW-GMOBBJLQSA-N Ile-Asp-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N UMYZBHKAVTXWIW-GMOBBJLQSA-N 0.000 description 1
- GAZGFPOZOLEYAJ-YTFOTSKYSA-N Ile-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N GAZGFPOZOLEYAJ-YTFOTSKYSA-N 0.000 description 1
- WSSGUVAKYCQSCT-XUXIUFHCSA-N Ile-Met-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)O)N WSSGUVAKYCQSCT-XUXIUFHCSA-N 0.000 description 1
- HQEPKOFULQTSFV-JURCDPSOSA-N Ile-Phe-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)O)N HQEPKOFULQTSFV-JURCDPSOSA-N 0.000 description 1
- JZNVOBUNTWNZPW-GHCJXIJMSA-N Ile-Ser-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N JZNVOBUNTWNZPW-GHCJXIJMSA-N 0.000 description 1
- VGSPNSSCMOHRRR-BJDJZHNGSA-N Ile-Ser-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N VGSPNSSCMOHRRR-BJDJZHNGSA-N 0.000 description 1
- ZDNNDIJTUHQCAM-MXAVVETBSA-N Ile-Ser-Phe Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N ZDNNDIJTUHQCAM-MXAVVETBSA-N 0.000 description 1
- JTBFQNHKNRZJDS-SYWGBEHUSA-N Ile-Trp-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](C)C(=O)O)N JTBFQNHKNRZJDS-SYWGBEHUSA-N 0.000 description 1
- 208000001718 Immediate Hypersensitivity Diseases 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 1
- 102100032999 Integrin beta-3 Human genes 0.000 description 1
- 108010020950 Integrin beta3 Proteins 0.000 description 1
- 102100036714 Interferon alpha/beta receptor 1 Human genes 0.000 description 1
- 102100035678 Interferon gamma receptor 1 Human genes 0.000 description 1
- 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
- 102100020881 Interleukin-1 alpha Human genes 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 108010082786 Interleukin-1alpha Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 102000010786 Interleukin-5 Receptors Human genes 0.000 description 1
- 108010038484 Interleukin-5 Receptors Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 1
- UGTHTQWIQKEDEH-BQBZGAKWSA-N L-alanyl-L-prolylglycine zwitterion Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UGTHTQWIQKEDEH-BQBZGAKWSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HFKJBCPRWWGPEY-BQBZGAKWSA-N L-arginyl-L-glutamic acid Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HFKJBCPRWWGPEY-BQBZGAKWSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 1
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 1
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- 108010054278 Lac Repressors Proteins 0.000 description 1
- 101710163560 Lamina-associated polypeptide 2, isoform alpha Proteins 0.000 description 1
- 101710189385 Lamina-associated polypeptide 2, isoforms beta/gamma Proteins 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 1
- SENJXOPIZNYLHU-IUCAKERBSA-N Leu-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-IUCAKERBSA-N 0.000 description 1
- MMEDVBWCMGRKKC-GARJFASQSA-N Leu-Asp-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N MMEDVBWCMGRKKC-GARJFASQSA-N 0.000 description 1
- DPWGZWUMUUJQDT-IUCAKERBSA-N Leu-Gln-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O DPWGZWUMUUJQDT-IUCAKERBSA-N 0.000 description 1
- RVVBWTWPNFDYBE-SRVKXCTJSA-N Leu-Glu-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVVBWTWPNFDYBE-SRVKXCTJSA-N 0.000 description 1
- NEEOBPIXKWSBRF-IUCAKERBSA-N Leu-Glu-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O NEEOBPIXKWSBRF-IUCAKERBSA-N 0.000 description 1
- BABSVXFGKFLIGW-UWVGGRQHSA-N Leu-Gly-Arg Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCNC(N)=N BABSVXFGKFLIGW-UWVGGRQHSA-N 0.000 description 1
- QPXBPQUGXHURGP-UWVGGRQHSA-N Leu-Gly-Met Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CCSC)C(=O)O)N QPXBPQUGXHURGP-UWVGGRQHSA-N 0.000 description 1
- BTNXKBVLWJBTNR-SRVKXCTJSA-N Leu-His-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(O)=O BTNXKBVLWJBTNR-SRVKXCTJSA-N 0.000 description 1
- KUIDCYNIEJBZBU-AJNGGQMLSA-N Leu-Ile-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O KUIDCYNIEJBZBU-AJNGGQMLSA-N 0.000 description 1
- QNBVTHNJGCOVFA-AVGNSLFASA-N Leu-Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O QNBVTHNJGCOVFA-AVGNSLFASA-N 0.000 description 1
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 1
- HVHRPWQEQHIQJF-AVGNSLFASA-N Leu-Lys-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O HVHRPWQEQHIQJF-AVGNSLFASA-N 0.000 description 1
- IDGZVZJLYFTXSL-DCAQKATOSA-N Leu-Ser-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IDGZVZJLYFTXSL-DCAQKATOSA-N 0.000 description 1
- AKVBOOKXVAMKSS-GUBZILKMSA-N Leu-Ser-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O AKVBOOKXVAMKSS-GUBZILKMSA-N 0.000 description 1
- ADJWHHZETYAAAX-SRVKXCTJSA-N Leu-Ser-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N ADJWHHZETYAAAX-SRVKXCTJSA-N 0.000 description 1
- ILDSIMPXNFWKLH-KATARQTJSA-N Leu-Thr-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ILDSIMPXNFWKLH-KATARQTJSA-N 0.000 description 1
- YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 1
- XOEDPXDZJHBQIX-ULQDDVLXSA-N Leu-Val-Phe Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XOEDPXDZJHBQIX-ULQDDVLXSA-N 0.000 description 1
- VKVDRTGWLVZJOM-DCAQKATOSA-N Leu-Val-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O VKVDRTGWLVZJOM-DCAQKATOSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 101000831620 Locusta migratoria Locustatachykinin-2 Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102100035304 Lymphotactin Human genes 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 description 1
- JGAMUXDWYSXYLM-SRVKXCTJSA-N Lys-Arg-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O JGAMUXDWYSXYLM-SRVKXCTJSA-N 0.000 description 1
- HIIZIQUUHIXUJY-GUBZILKMSA-N Lys-Asp-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HIIZIQUUHIXUJY-GUBZILKMSA-N 0.000 description 1
- MWVUEPNEPWMFBD-SRVKXCTJSA-N Lys-Cys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CCCCN MWVUEPNEPWMFBD-SRVKXCTJSA-N 0.000 description 1
- DRCILAJNUJKAHC-SRVKXCTJSA-N Lys-Glu-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DRCILAJNUJKAHC-SRVKXCTJSA-N 0.000 description 1
- DCRWPTBMWMGADO-AVGNSLFASA-N Lys-Glu-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DCRWPTBMWMGADO-AVGNSLFASA-N 0.000 description 1
- GHOIOYHDDKXIDX-SZMVWBNQSA-N Lys-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCCCN)C(O)=O)=CNC2=C1 GHOIOYHDDKXIDX-SZMVWBNQSA-N 0.000 description 1
- XNKDCYABMBBEKN-IUCAKERBSA-N Lys-Gly-Gln Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O XNKDCYABMBBEKN-IUCAKERBSA-N 0.000 description 1
- IOQWIOPSKJOEKI-SRVKXCTJSA-N Lys-Ser-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IOQWIOPSKJOEKI-SRVKXCTJSA-N 0.000 description 1
- YKBSXQFZWFXFIB-VOAKCMCISA-N Lys-Thr-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O YKBSXQFZWFXFIB-VOAKCMCISA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 108010036176 Melitten Proteins 0.000 description 1
- LMKSBGIUPVRHEH-FXQIFTODSA-N Met-Ala-Asn Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(N)=O LMKSBGIUPVRHEH-FXQIFTODSA-N 0.000 description 1
- UASDAHIAHBRZQV-YUMQZZPRSA-N Met-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N UASDAHIAHBRZQV-YUMQZZPRSA-N 0.000 description 1
- CTVJSFRHUOSCQQ-DCAQKATOSA-N Met-Arg-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O CTVJSFRHUOSCQQ-DCAQKATOSA-N 0.000 description 1
- KQBJYJXPZBNEIK-DCAQKATOSA-N Met-Glu-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQBJYJXPZBNEIK-DCAQKATOSA-N 0.000 description 1
- PHKBGZKVOJCIMZ-SRVKXCTJSA-N Met-Pro-Arg Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PHKBGZKVOJCIMZ-SRVKXCTJSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100000659 Mus musculus Ackr1 gene Proteins 0.000 description 1
- 101000610625 Mus musculus Serine protease 33 Proteins 0.000 description 1
- 101100207071 Mus musculus Tnfsf8 gene Proteins 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical class ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- WYBVBIHNJWOLCJ-UHFFFAOYSA-N N-L-arginyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCCN=C(N)N WYBVBIHNJWOLCJ-UHFFFAOYSA-N 0.000 description 1
- SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 description 1
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 108010066427 N-valyltryptophan Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 description 1
- 102100031248 Patatin-like phospholipase domain-containing protein 2 Human genes 0.000 description 1
- OZILORBBPKKGRI-RYUDHWBXSA-N Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 OZILORBBPKKGRI-RYUDHWBXSA-N 0.000 description 1
- VHWOBXIWBDWZHK-IHRRRGAJSA-N Phe-Arg-Asp Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 VHWOBXIWBDWZHK-IHRRRGAJSA-N 0.000 description 1
- MPGJIHFJCXTVEX-KKUMJFAQSA-N Phe-Arg-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O MPGJIHFJCXTVEX-KKUMJFAQSA-N 0.000 description 1
- UEHNWRNADDPYNK-DLOVCJGASA-N Phe-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CC=CC=C1)N UEHNWRNADDPYNK-DLOVCJGASA-N 0.000 description 1
- PDUVELWDJZOUEI-IHRRRGAJSA-N Phe-Cys-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PDUVELWDJZOUEI-IHRRRGAJSA-N 0.000 description 1
- ALHULIGNEXGFRM-QWRGUYRKSA-N Phe-Cys-Gly Chemical compound OC(=O)CNC(=O)[C@H](CS)NC(=O)[C@@H](N)CC1=CC=CC=C1 ALHULIGNEXGFRM-QWRGUYRKSA-N 0.000 description 1
- OWCLJDXHHZUNEL-IHRRRGAJSA-N Phe-Cys-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O OWCLJDXHHZUNEL-IHRRRGAJSA-N 0.000 description 1
- HOYQLNNGMHXZDW-KKUMJFAQSA-N Phe-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O HOYQLNNGMHXZDW-KKUMJFAQSA-N 0.000 description 1
- GYEPCBNTTRORKW-PCBIJLKTSA-N Phe-Ile-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O GYEPCBNTTRORKW-PCBIJLKTSA-N 0.000 description 1
- MSHZERMPZKCODG-ACRUOGEOSA-N Phe-Leu-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 MSHZERMPZKCODG-ACRUOGEOSA-N 0.000 description 1
- OAOLATANIHTNCZ-IHRRRGAJSA-N Phe-Met-Asp Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N OAOLATANIHTNCZ-IHRRRGAJSA-N 0.000 description 1
- IIEOLPMQYRBZCN-SRVKXCTJSA-N Phe-Ser-Cys Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O IIEOLPMQYRBZCN-SRVKXCTJSA-N 0.000 description 1
- GOUWCZRDTWTODO-YDHLFZDLSA-N Phe-Val-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O GOUWCZRDTWTODO-YDHLFZDLSA-N 0.000 description 1
- 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 description 1
- 229920001363 Polidocanol Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
- 229920000037 Polyproline Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 229920002642 Polysorbate 65 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- OLHDPZMYUSBGDE-GUBZILKMSA-N Pro-Arg-Cys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O OLHDPZMYUSBGDE-GUBZILKMSA-N 0.000 description 1
- ICTZKEXYDDZZFP-SRVKXCTJSA-N Pro-Arg-Pro Chemical compound N([C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(O)=O)C(=O)[C@@H]1CCCN1 ICTZKEXYDDZZFP-SRVKXCTJSA-N 0.000 description 1
- TUYWCHPXKQTISF-LPEHRKFASA-N Pro-Cys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N2CCC[C@@H]2C(=O)O TUYWCHPXKQTISF-LPEHRKFASA-N 0.000 description 1
- PULPZRAHVFBVTO-DCAQKATOSA-N Pro-Glu-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PULPZRAHVFBVTO-DCAQKATOSA-N 0.000 description 1
- HAAQQNHQZBOWFO-LURJTMIESA-N Pro-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1 HAAQQNHQZBOWFO-LURJTMIESA-N 0.000 description 1
- SXMSEHDMNIUTSP-DCAQKATOSA-N Pro-Lys-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O SXMSEHDMNIUTSP-DCAQKATOSA-N 0.000 description 1
- ZLXKLMHAMDENIO-DCAQKATOSA-N Pro-Lys-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLXKLMHAMDENIO-DCAQKATOSA-N 0.000 description 1
- YYARMJSFDLIDFS-FKBYEOEOSA-N Pro-Phe-Trp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O YYARMJSFDLIDFS-FKBYEOEOSA-N 0.000 description 1
- PCWLNNZTBJTZRN-AVGNSLFASA-N Pro-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 PCWLNNZTBJTZRN-AVGNSLFASA-N 0.000 description 1
- GOMUXSCOIWIJFP-GUBZILKMSA-N Pro-Ser-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GOMUXSCOIWIJFP-GUBZILKMSA-N 0.000 description 1
- OIDKVWTWGDWMHY-RYUDHWBXSA-N Pro-Tyr Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1NCCC1)C1=CC=C(O)C=C1 OIDKVWTWGDWMHY-RYUDHWBXSA-N 0.000 description 1
- YDTUEBLEAVANFH-RCWTZXSCSA-N Pro-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 YDTUEBLEAVANFH-RCWTZXSCSA-N 0.000 description 1
- 101710083689 Probable capsid protein Proteins 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102100028564 Protein phosphatase 1 regulatory subunit 42 Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- 230000010799 Receptor Interactions Effects 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 102000000395 SH3 domains Human genes 0.000 description 1
- 108050008861 SH3 domains Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000235088 Saccharomyces sp. Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 108090000184 Selectins Proteins 0.000 description 1
- 102000003800 Selectins Human genes 0.000 description 1
- YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 description 1
- RZEQTVHJZCIUBT-WDSKDSINSA-N Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N RZEQTVHJZCIUBT-WDSKDSINSA-N 0.000 description 1
- VGNYHOBZJKWRGI-CIUDSAMLSA-N Ser-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO VGNYHOBZJKWRGI-CIUDSAMLSA-N 0.000 description 1
- VBKBDLMWICBSCY-IMJSIDKUSA-N Ser-Asp Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O VBKBDLMWICBSCY-IMJSIDKUSA-N 0.000 description 1
- BNFVPSRLHHPQKS-WHFBIAKZSA-N Ser-Asp-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O BNFVPSRLHHPQKS-WHFBIAKZSA-N 0.000 description 1
- YPUSXTWURJANKF-KBIXCLLPSA-N Ser-Gln-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O YPUSXTWURJANKF-KBIXCLLPSA-N 0.000 description 1
- VDVYTKZBMFADQH-AVGNSLFASA-N Ser-Gln-Tyr Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 VDVYTKZBMFADQH-AVGNSLFASA-N 0.000 description 1
- PVDTYLHUWAEYGY-CIUDSAMLSA-N Ser-Glu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PVDTYLHUWAEYGY-CIUDSAMLSA-N 0.000 description 1
- DJACUBDEDBZKLQ-KBIXCLLPSA-N Ser-Ile-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O DJACUBDEDBZKLQ-KBIXCLLPSA-N 0.000 description 1
- XXNYYSXNXCJYKX-DCAQKATOSA-N Ser-Leu-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O XXNYYSXNXCJYKX-DCAQKATOSA-N 0.000 description 1
- GZSZPKSBVAOGIE-CIUDSAMLSA-N Ser-Lys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O GZSZPKSBVAOGIE-CIUDSAMLSA-N 0.000 description 1
- STIAINRLUUKYKM-WFBYXXMGSA-N Ser-Trp-Ala Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CO)=CNC2=C1 STIAINRLUUKYKM-WFBYXXMGSA-N 0.000 description 1
- FVFUOQIYDPAIJR-XIRDDKMYSA-N Ser-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CO)N FVFUOQIYDPAIJR-XIRDDKMYSA-N 0.000 description 1
- IAOHCSQDQDWRQU-GUBZILKMSA-N Ser-Val-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IAOHCSQDQDWRQU-GUBZILKMSA-N 0.000 description 1
- BEBVVQPDSHHWQL-NRPADANISA-N Ser-Val-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O BEBVVQPDSHHWQL-NRPADANISA-N 0.000 description 1
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 235000015125 Sterculia urens Nutrition 0.000 description 1
- 240000001058 Sterculia urens Species 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 1
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 101150029803 TMP gene Proteins 0.000 description 1
- 108700012411 TNFSF10 Proteins 0.000 description 1
- TYVAWPFQYFPSBR-BFHQHQDPSA-N Thr-Ala-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)NCC(O)=O TYVAWPFQYFPSBR-BFHQHQDPSA-N 0.000 description 1
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 1
- HYLXOQURIOCKIH-VQVTYTSYSA-N Thr-Arg Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N HYLXOQURIOCKIH-VQVTYTSYSA-N 0.000 description 1
- UKBSDLHIKIXJKH-HJGDQZAQSA-N Thr-Arg-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O UKBSDLHIKIXJKH-HJGDQZAQSA-N 0.000 description 1
- CEXFELBFVHLYDZ-XGEHTFHBSA-N Thr-Arg-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CEXFELBFVHLYDZ-XGEHTFHBSA-N 0.000 description 1
- OJRNZRROAIAHDL-LKXGYXEUSA-N Thr-Asn-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OJRNZRROAIAHDL-LKXGYXEUSA-N 0.000 description 1
- KWQBJOUOSNJDRR-XAVMHZPKSA-N Thr-Cys-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N)O KWQBJOUOSNJDRR-XAVMHZPKSA-N 0.000 description 1
- DSLHSTIUAPKERR-XGEHTFHBSA-N Thr-Cys-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O DSLHSTIUAPKERR-XGEHTFHBSA-N 0.000 description 1
- DKDHTRVDOUZZTP-IFFSRLJSSA-N Thr-Gln-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)[C@@H](C)O)C(O)=O DKDHTRVDOUZZTP-IFFSRLJSSA-N 0.000 description 1
- FHDLKMFZKRUQCE-HJGDQZAQSA-N Thr-Glu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FHDLKMFZKRUQCE-HJGDQZAQSA-N 0.000 description 1
- VULNJDORNLBPNG-SWRJLBSHSA-N Thr-Glu-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O VULNJDORNLBPNG-SWRJLBSHSA-N 0.000 description 1
- MSIYNSBKKVMGFO-BHNWBGBOSA-N Thr-Gly-Pro Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N1CCC[C@@H]1C(=O)O)N)O MSIYNSBKKVMGFO-BHNWBGBOSA-N 0.000 description 1
- AHOLTQCAVBSUDP-PPCPHDFISA-N Thr-Ile-Lys Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O AHOLTQCAVBSUDP-PPCPHDFISA-N 0.000 description 1
- MEJHFIOYJHTWMK-VOAKCMCISA-N Thr-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)[C@@H](C)O MEJHFIOYJHTWMK-VOAKCMCISA-N 0.000 description 1
- NCXVJIQMWSGRHY-KXNHARMFSA-N Thr-Leu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O NCXVJIQMWSGRHY-KXNHARMFSA-N 0.000 description 1
- YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 description 1
- BDGBHYCAZJPLHX-HJGDQZAQSA-N Thr-Lys-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O BDGBHYCAZJPLHX-HJGDQZAQSA-N 0.000 description 1
- MGJLBZFUXUGMML-VOAKCMCISA-N Thr-Lys-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MGJLBZFUXUGMML-VOAKCMCISA-N 0.000 description 1
- ABWNZPOIUJMNKT-IXOXFDKPSA-N Thr-Phe-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O ABWNZPOIUJMNKT-IXOXFDKPSA-N 0.000 description 1
- XKWABWFMQXMUMT-HJGDQZAQSA-N Thr-Pro-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XKWABWFMQXMUMT-HJGDQZAQSA-N 0.000 description 1
- GXDLGHLJTHMDII-WISUUJSJSA-N Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(O)=O GXDLGHLJTHMDII-WISUUJSJSA-N 0.000 description 1
- NDZYTIMDOZMECO-SHGPDSBTSA-N Thr-Thr-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O NDZYTIMDOZMECO-SHGPDSBTSA-N 0.000 description 1
- NLWDSYKZUPRMBJ-IEGACIPQSA-N Thr-Trp-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(C)C)C(=O)O)N)O NLWDSYKZUPRMBJ-IEGACIPQSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102400000159 Thymopoietin Human genes 0.000 description 1
- 239000000898 Thymopoietin Substances 0.000 description 1
- 101000805609 Tityus fasciolatus Venom metalloproteinase antarease-like TfasMP_A Proteins 0.000 description 1
- 101000805582 Tityus pachyurus Venom metalloproteinase antarease-like TpachMP_A Proteins 0.000 description 1
- 101000805584 Tityus pachyurus Venom metalloproteinase antarease-like TpachMP_B Proteins 0.000 description 1
- 101000805583 Tityus serrulatus Venom metalloproteinase antarease TserMP_A Proteins 0.000 description 1
- 101000805574 Tityus serrulatus Venom metalloproteinase antarease-like TserMP_B Proteins 0.000 description 1
- 101000805580 Tityus trivittatus Venom metalloproteinase antarease-like TtrivMP_A Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- LCPVBXOHXMBLFW-JSGCOSHPSA-N Trp-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)=CNC2=C1 LCPVBXOHXMBLFW-JSGCOSHPSA-N 0.000 description 1
- HYNAKPYFEYJMAS-XIRDDKMYSA-N Trp-Arg-Glu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HYNAKPYFEYJMAS-XIRDDKMYSA-N 0.000 description 1
- NBHGNEJMBNQQKZ-UBHSHLNASA-N Trp-Asp-Cys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N NBHGNEJMBNQQKZ-UBHSHLNASA-N 0.000 description 1
- DQDXHYIEITXNJY-BPUTZDHNSA-N Trp-Gln-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N DQDXHYIEITXNJY-BPUTZDHNSA-N 0.000 description 1
- PKUJMYZNJMRHEZ-XIRDDKMYSA-N Trp-Glu-Arg Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PKUJMYZNJMRHEZ-XIRDDKMYSA-N 0.000 description 1
- UDCHKDYNMRJYMI-QEJZJMRPSA-N Trp-Glu-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O UDCHKDYNMRJYMI-QEJZJMRPSA-N 0.000 description 1
- SNJAPSVIPKUMCK-NWLDYVSISA-N Trp-Glu-Thr Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SNJAPSVIPKUMCK-NWLDYVSISA-N 0.000 description 1
- SAKLWFSRZTZQAJ-GQGQLFGLSA-N Trp-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N SAKLWFSRZTZQAJ-GQGQLFGLSA-N 0.000 description 1
- IQXWAJUIAQLZNX-IHPCNDPISA-N Trp-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N IQXWAJUIAQLZNX-IHPCNDPISA-N 0.000 description 1
- RRVUOLRWIZXBRQ-IHPCNDPISA-N Trp-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N RRVUOLRWIZXBRQ-IHPCNDPISA-N 0.000 description 1
- RWAYYYOZMHMEGD-XIRDDKMYSA-N Trp-Leu-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 RWAYYYOZMHMEGD-XIRDDKMYSA-N 0.000 description 1
- MEZCXKYMMQJRDE-PMVMPFDFSA-N Trp-Leu-Tyr Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)CC(C)C)C(O)=O)C1=CC=C(O)C=C1 MEZCXKYMMQJRDE-PMVMPFDFSA-N 0.000 description 1
- LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 description 1
- RNDWCRUOGGQDKN-UBHSHLNASA-N Trp-Ser-Asp Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RNDWCRUOGGQDKN-UBHSHLNASA-N 0.000 description 1
- WSMVEHPVOYXPAQ-XIRDDKMYSA-N Trp-Ser-Lys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N WSMVEHPVOYXPAQ-XIRDDKMYSA-N 0.000 description 1
- 101710113414 Tumor necrosis factor ligand superfamily member 8 Proteins 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 206010045240 Type I hypersensitivity Diseases 0.000 description 1
- QJBWZNTWJSZUOY-UWJYBYFXSA-N Tyr-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N QJBWZNTWJSZUOY-UWJYBYFXSA-N 0.000 description 1
- JXNRXNCCROJZFB-RYUDHWBXSA-N Tyr-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 JXNRXNCCROJZFB-RYUDHWBXSA-N 0.000 description 1
- HTHCZRWCFXMENJ-KKUMJFAQSA-N Tyr-Arg-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HTHCZRWCFXMENJ-KKUMJFAQSA-N 0.000 description 1
- WDIJBEWLXLQQKD-ULQDDVLXSA-N Tyr-Arg-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O WDIJBEWLXLQQKD-ULQDDVLXSA-N 0.000 description 1
- SMLCYZYQFRTLCO-UWJYBYFXSA-N Tyr-Cys-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O SMLCYZYQFRTLCO-UWJYBYFXSA-N 0.000 description 1
- MOCXXGZHHSPNEJ-AVGNSLFASA-N Tyr-Cys-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O MOCXXGZHHSPNEJ-AVGNSLFASA-N 0.000 description 1
- FFCRCJZJARTYCG-KKUMJFAQSA-N Tyr-Cys-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O)N)O FFCRCJZJARTYCG-KKUMJFAQSA-N 0.000 description 1
- ZAGPDPNPWYPEIR-SRVKXCTJSA-N Tyr-Cys-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O ZAGPDPNPWYPEIR-SRVKXCTJSA-N 0.000 description 1
- BODHJXJNRVRKFA-BZSNNMDCSA-N Tyr-Cys-Tyr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BODHJXJNRVRKFA-BZSNNMDCSA-N 0.000 description 1
- XQYHLZNPOTXRMQ-KKUMJFAQSA-N Tyr-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XQYHLZNPOTXRMQ-KKUMJFAQSA-N 0.000 description 1
- OHNXAUCZVWGTLL-KKUMJFAQSA-N Tyr-His-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CS)C(=O)O)N)O OHNXAUCZVWGTLL-KKUMJFAQSA-N 0.000 description 1
- VTCKHZJKWQENKX-KBPBESRZSA-N Tyr-Lys-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O VTCKHZJKWQENKX-KBPBESRZSA-N 0.000 description 1
- SINRIKQYQJRGDQ-MEYUZBJRSA-N Tyr-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SINRIKQYQJRGDQ-MEYUZBJRSA-N 0.000 description 1
- QMNWABHLJOHGDS-IHRRRGAJSA-N Tyr-Met-Cys Chemical compound SC[C@@H](C(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 QMNWABHLJOHGDS-IHRRRGAJSA-N 0.000 description 1
- NHOVZGFNTGMYMI-KKUMJFAQSA-N Tyr-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NHOVZGFNTGMYMI-KKUMJFAQSA-N 0.000 description 1
- RIVVDNTUSRVTQT-IRIUXVKKSA-N Tyr-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O RIVVDNTUSRVTQT-IRIUXVKKSA-N 0.000 description 1
- XTOCLOATLKOZAU-JBACZVJFSA-N Tyr-Trp-Glu Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N XTOCLOATLKOZAU-JBACZVJFSA-N 0.000 description 1
- MQUYPYFPHIPVHJ-MNSWYVGCSA-N Tyr-Trp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)O MQUYPYFPHIPVHJ-MNSWYVGCSA-N 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- ASQFIHTXXMFENG-XPUUQOCRSA-N Val-Ala-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O ASQFIHTXXMFENG-XPUUQOCRSA-N 0.000 description 1
- IBIDRSSEHFLGSD-YUMQZZPRSA-N Val-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-YUMQZZPRSA-N 0.000 description 1
- KKHRWGYHBZORMQ-NHCYSSNCSA-N Val-Arg-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKHRWGYHBZORMQ-NHCYSSNCSA-N 0.000 description 1
- QHDXUYOYTPWCSK-RCOVLWMOSA-N Val-Asp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N QHDXUYOYTPWCSK-RCOVLWMOSA-N 0.000 description 1
- OUUBKKIJQIAPRI-LAEOZQHASA-N Val-Gln-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O OUUBKKIJQIAPRI-LAEOZQHASA-N 0.000 description 1
- BRPKEERLGYNCNC-NHCYSSNCSA-N Val-Glu-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N BRPKEERLGYNCNC-NHCYSSNCSA-N 0.000 description 1
- NXRAUQGGHPCJIB-RCOVLWMOSA-N Val-Gly-Asn Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O NXRAUQGGHPCJIB-RCOVLWMOSA-N 0.000 description 1
- XXROXFHCMVXETG-UWVGGRQHSA-N Val-Gly-Val Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O XXROXFHCMVXETG-UWVGGRQHSA-N 0.000 description 1
- XTDDIVQWDXMRJL-IHRRRGAJSA-N Val-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N XTDDIVQWDXMRJL-IHRRRGAJSA-N 0.000 description 1
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-N 0.000 description 1
- HPANGHISDXDUQY-ULQDDVLXSA-N Val-Lys-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N HPANGHISDXDUQY-ULQDDVLXSA-N 0.000 description 1
- UEPLNXPLHJUYPT-AVGNSLFASA-N Val-Met-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(O)=O UEPLNXPLHJUYPT-AVGNSLFASA-N 0.000 description 1
- PWCJARIQERIIGF-BZSNNMDCSA-N Val-Met-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N PWCJARIQERIIGF-BZSNNMDCSA-N 0.000 description 1
- LJSZPMSUYKKKCP-UBHSHLNASA-N Val-Phe-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 LJSZPMSUYKKKCP-UBHSHLNASA-N 0.000 description 1
- HJSLDXZAZGFPDK-ULQDDVLXSA-N Val-Phe-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C(C)C)N HJSLDXZAZGFPDK-ULQDDVLXSA-N 0.000 description 1
- MNSSBIHFEUUXNW-RCWTZXSCSA-N Val-Thr-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N MNSSBIHFEUUXNW-RCWTZXSCSA-N 0.000 description 1
- UQMPYVLTQCGRSK-IFFSRLJSSA-N Val-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N)O UQMPYVLTQCGRSK-IFFSRLJSSA-N 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 208000006110 Wiskott-Aldrich syndrome Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- ULCUCJFASIJEOE-NPECTJMMSA-N adrenomedullin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H]1C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)[C@@H](C)O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 ULCUCJFASIJEOE-NPECTJMMSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000012387 aerosolization Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 238000003314 affinity selection Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 1
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003831 antifriction material Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 108010001271 arginyl-glutamyl-arginine Proteins 0.000 description 1
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 1
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 108010060035 arginylproline Proteins 0.000 description 1
- 108010036533 arginylvaline Proteins 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000011021 bench scale process Methods 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 238000005864 bromoacetylation reaction Methods 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229910000394 calcium triphosphate Inorganic materials 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
- 230000010405 clearance mechanism Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical compound O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 1
- 108010016616 cysteinylglycine Proteins 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000003182 dose-response assay Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 108010025752 echistatin Proteins 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 231100000562 fetal loss Toxicity 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 229910021485 fumed silica Inorganic materials 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 108010085059 glutamyl-arginyl-proline Proteins 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- JYPCXBJRLBHWME-UHFFFAOYSA-N glycyl-L-prolyl-L-arginine Natural products NCC(=O)N1CCCC1C(=O)NC(CCCN=C(N)N)C(O)=O JYPCXBJRLBHWME-UHFFFAOYSA-N 0.000 description 1
- 108010062266 glycyl-glycyl-argininal Proteins 0.000 description 1
- 108010026364 glycyl-glycyl-leucine Proteins 0.000 description 1
- 108010010096 glycyl-glycyl-tyrosine Proteins 0.000 description 1
- 108010078326 glycyl-glycyl-valine Proteins 0.000 description 1
- 108010025801 glycyl-prolyl-arginine Proteins 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 108010036413 histidylglycine Proteins 0.000 description 1
- 108010018006 histidylserine Proteins 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000054764 human MPL Human genes 0.000 description 1
- 102000053400 human TPO Human genes 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008102 immune modulation Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 108010078274 isoleucylvaline Proteins 0.000 description 1
- 108010053037 kyotorphin Proteins 0.000 description 1
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
- 101150109249 lacI gene Proteins 0.000 description 1
- 238000004989 laser desorption mass spectroscopy Methods 0.000 description 1
- 229950006462 lauromacrogol 400 Drugs 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 108010000761 leucylarginine Proteins 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 108010019677 lymphotactin Proteins 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 108010017391 lysylvaline Proteins 0.000 description 1
- 208000032345 macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 description 1
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- VDXZNPDIRNWWCW-UHFFFAOYSA-N melitten Chemical compound NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC(C)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NCC(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(C)CC)C(=O)NC(CO)C(=O)NC(C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-UHFFFAOYSA-N 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- YCXSYMVGMXQYNT-UHFFFAOYSA-N methyl 3-[(4-azidophenyl)disulfanyl]propanimidate Chemical compound COC(=N)CCSSC1=CC=C(N=[N+]=[N-])C=C1 YCXSYMVGMXQYNT-UHFFFAOYSA-N 0.000 description 1
- RMAHPRNLQIRHIJ-UHFFFAOYSA-N methyl carbamimidate Chemical compound COC(N)=N RMAHPRNLQIRHIJ-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- NEGQCMNHXHSFGU-UHFFFAOYSA-N methyl pyridine-2-carboximidate Chemical compound COC(=N)C1=CC=CC=N1 NEGQCMNHXHSFGU-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000006351 negative regulation of hormone secretion Effects 0.000 description 1
- 230000023837 negative regulation of proteolysis Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000008184 oral solid dosage form Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- CTVQQQPWNOVEAG-QDOPKCMFSA-N pardaxin Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CN)C1=CC=CC=C1 CTVQQQPWNOVEAG-QDOPKCMFSA-N 0.000 description 1
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 description 1
- RFWLACFDYFIVMC-UHFFFAOYSA-D pentacalcium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O RFWLACFDYFIVMC-UHFFFAOYSA-D 0.000 description 1
- 230000003094 perturbing effect Effects 0.000 description 1
- 108010083127 phage repressor proteins Proteins 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 108010089198 phenylalanyl-prolyl-arginine Proteins 0.000 description 1
- 108010024607 phenylalanylalanine Proteins 0.000 description 1
- 108010018625 phenylalanylarginine Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 238000000206 photolithography Methods 0.000 description 1
- 229940081066 picolinic acid Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
- 108010087782 poly(glycyl-alanyl) Proteins 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 108010002543 polyethylene glycol-recombinant human megakaryocyte growth and development factor Proteins 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
- 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
- 108010026466 polyproline Proteins 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940099511 polysorbate 65 Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 108010017378 prolyl aminopeptidase Proteins 0.000 description 1
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 1
- 108010079317 prolyl-tyrosine Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000029983 protein stabilization Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 229960003581 pyridoxal Drugs 0.000 description 1
- 235000008164 pyridoxal Nutrition 0.000 description 1
- 239000011674 pyridoxal Substances 0.000 description 1
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 1
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 1
- 229960001327 pyridoxal phosphate Drugs 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 235000021309 simple sugar Nutrition 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical group [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- LZWUCYAVMIKMIA-UHFFFAOYSA-M sodium;1-[3-[2-[(4-azido-2,3,5,6-tetrafluorobenzoyl)amino]ethyldisulfanyl]propanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCSSCCNC(=O)C1=C(F)C(F)=C(N=[N+]=[N-])C(F)=C1F LZWUCYAVMIKMIA-UHFFFAOYSA-M 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 108010061238 threonyl-glycine Proteins 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 230000001361 thrombopoietic effect Effects 0.000 description 1
- 108010059728 thrombopoietin mimetic peptide Proteins 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 108010036775 thymic humoral factor gamma 2 Proteins 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 108010015666 tryptophyl-leucyl-glutamic acid Proteins 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000009959 type I hypersensitivity Effects 0.000 description 1
- 108010079202 tyrosyl-alanyl-cysteine Proteins 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000012178 vegetable wax Substances 0.000 description 1
- 229940070384 ventolin Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 1
- 230000007279 water homeostasis Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229930195727 α-lactose Natural products 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6489—Metalloendopeptidases (3.4.24)
- C12N9/6491—Matrix metalloproteases [MMP's], e.g. interstitial collagenase (3.4.24.7); Stromelysins (3.4.24.17; 3.2.1.22); Matrilysin (3.4.24.23)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/524—Thrombopoietin, i.e. C-MPL ligand
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/525—Tumour necrosis factor [TNF]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/545—IL-1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- C07K14/8146—Metalloprotease (E.C. 3.4.24) inhibitors, e.g. tissue inhibitor of metallo proteinase, TIMP
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Definitions
- Antibodies comprise two functionally independent parts, a variable domain known as “Fab”, which binds antigen, and a constant domain known as “Fc”, which links to such effector functions as complement activation and attack by phagocytic cells.
- Fab variable domain
- Fc constant domain
- An Fc has a long serum half-life, whereas an Fab is short-lived.
- Structural analysis of protein-protein interaction may also be used to suggest peptides that mimic the binding activity of large protein ligands.
- the crystal structure may suggest the identity and relative orientation of critical residues of the large protein ligand, from which a peptide may be designed. See, e.g., Takasaki et al. (1997), Nature Biotech. 15: 1266-70.
- These analytical methods may also be used to investigate the interaction between a receptor protein and peptides selected by phage display, which may suggest further modification of the peptides to increase binding affinity.
- C4BP C4BP protein 272: 14658-65 linear urokinase processes associated with Goodson et al. (1994), receptor urokinase interaction with Proc. Natl. Acad. Sci. 91: its receptor (e.g., 7129-33; International angiogenesis, tumor cell application WO invasion and metastasis); 97/35969, published (“UKR antagonist”) Oct. 2, 1997 linear Mdm2, Hdm2 Inhibition of inactivation of Picksley et al. (1994), p53 mediated by Mdm2 or Oncogene 9: 2523-9; hdm2; anti-tumor Bottger et al. (1997) J. Mol. Biol.
- the compounds of this invention may be used for therapeutic or prophylactic purposes by formulating them with appropriate pharmaceutical carrier materials and administering an effective amount to a patient, such as a human (or other mammal) in need thereof.
- a patient such as a human (or other mammal) in need thereof.
- Other related aspects are also included in the instant invention.
- A, D Single disulfide-bonded dimers.
- IgG1 antibodies typically have two disulfide bonds at the hinge region between the constant and variable domains.
- the Fc domain in FIGS. 2A and 2D may be formed by truncation between the two disulfide bond sites or by substitution of a cysteinyl residue with an unreactive residue (e.g., alanyl).
- the Fc domain is linked at the amino terminus of the peptides; in 2 D, at the carboxyl terminus.
- B, E Doubly disulfide-bonded dimers.
- This Fc domain may be formed by truncation of the parent antibody to retain both cysteinyl residues in the Fc domain chains or by expression from a construct including a sequence encoding such an Fc domain.
- the Fc domain is linked at the amino terminus of the peptides; in 2 E, at the carboxyl terminus.
- dimers may be formed by using Fc domains derived from different types of antibodies (e.g., IgG2, IgM).
- FIGS. 25A and 25B show the nucleotide and amino acid sequences (SEQ ID NOS: 1067 and 1068) of the Fc-MMP inhibitor fusion molecule described in Example 7 hereinafter.
- the term “-antagonist peptide” or “inhibitor peptide” refers to a peptide that blocks or in some way interferes with the biological activity of the associated protein of interest, or has biological activity comparable to a known antagonist or inhibitor of the associated protein of interest.
- the term “TNF-antagonist peptide” comprises peptides that can be identified or derived as described in Takasaki et al. (1997), Nature Biotech. 15: 1266-70 or any of the references in Table 2 identified as having TNF-antagonistic subject matter. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- IL-1 antagonist and “IL-1ra-mimetic peptide” comprises peptides that inhibit or down-regulate activation of the IL-1 receptor by IL-1.
- IL-1 receptor activation results from formation of a complex among IL-1, IL-1 receptor, and IL-1 receptor accessory protein.
- IL-1 antagonist or IL-1ra-mimetic peptides bind to IL-1, IL-1 receptor, or IL-1 receptor accessory protein and obstruct complex formation among any two or three components of the complex.
- Exemplary IL-1 antagonist or IL-1ra-mimetic peptides can be identified or derived as described in U.S. Pat. Nos.
- VEGF-antagonist peptide comprises peptides that can be identified or derived as described in Fairbrother (1998), Biochem. 37: 17754-64, and in any of the references in Table 2 identified as having VEGF-antagonistic subject matter. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- Exemplary peptides for this invention appear in Tables 4 through 20 below. These peptides may be prepared by methods disclosed in the art. Single letter amino acid abbreviations are used. The X in these sequences (and throughout this specification, unless specified otherwise in a particular instance) means that any of the 20 naturally occurring amino acid residues may be present. Any of these peptides may be linked in tandem (i.e., sequentially), with or without linkers, and a few tandem-linked examples are provided in the table. Linkers are listed as “A” and may be any of the linkers described herein. Tandem repeats and linkers are shown separated by dashes for clarity.
- Derivatized peptides in the tables are exemplary rather than limiting, as the associated underivatized peptides may be employed in this invention, as well.
- the capping amino group is shown as —NH 2 .
- amino acid residues are substituted by moieties other than amino acid residues
- the substitutions are denoted by ⁇ , which signifies any of the moieties described in Bhatnagar et al. (1996), J. Med. Chem. 39: 3814-9 and Cuthbertson et al. (1997), T. Med. Chem. 40: 2876-82, which are incorporated by reference.
- One or more individual amino acid residues is modified.
- Various derivatizing agents are known to react specifically with selected sidechains or terminal residues, as described in detail below.
- Carboxyl sidechain groups may be selectively modified by reaction with carbodiimides (R 1 -N ⁇ C ⁇ N—R′) such as 1-cyclohexyl-3-(2-morpholinyl-(4-ethyl) carbodiimide or 1-ethyl-3-(4-azonia-4,4-dimethylpentyl) carbodiimide.
- carbodiimides R 1 -N ⁇ C ⁇ N—R′
- aspartyl and glutamyl residues may be converted to asparaginyl and glutaminyl residues by reaction with ammonium ions.
- the conditions to be treated are generally those that involve an existing megakaryocyte/platelet deficiency or an expected megakaryocyte/platelet deficiency (e.g., because of planned surgery or platelet donation). Such conditions will usually be the result of a deficiency (temporary or permanent) of active Mpl ligand in vivo.
- the generic term for platelet deficiency is thrombocytopenia, and hence the methods and compositions of the present invention are generally available for treating thrombocytopenia in patients in need thereof.
- Thrombocytopenia may be present for various reasons, including chemotherapy and other therapy with a variety of drugs, radiation therapy, surgery, accidental blood loss, and other specific disease conditions.
- Exemplary specific disease conditions that involve thrombocytopenia and may be treated in accordance with this invention are: aplastic anemia, idiopathic thrombocy openia, metastatic tumors which result in thrombocytopenia, systemic lupus erythematosus, splenomegaly, Fanconi's syndrome, vitamin B12 deficiency, folic acid deficiency, May-Hegglin anomaly, Wiskott-Aldrich syndrome, and paroxysmal nocturnal hemoglobinuria.
- certain treatments for AIDS result in thrombocytopenia (e.g., AZT).
- Certain wound healing disorders might also benefit from an increase in platelet numbers.
- the TPO-mimetic compounds of this invention may be used in any situation in which production of platelets or platelet precursor cells is desired, or in which stimulation of the c-Mpl receptor is desired.
- the compounds of this invention may be used to treat any condition in a mammal wherein there is a need of platelets, megakaryocytes, and the like. Such conditions are described in detail in the following exemplary sources: WO95/26746; WO95/21919; WO95/18858; WO95/21920 and are incorporated herein.
- This duplex was amplified in a PCR reaction using 1830-52 and 1830-55 as the sense and antisense primers.
- the Fc portion of the molecule was generated in a PCR reaction with pFc-A3 using the primers 1216-52 and 1830-51 as described above for Fc-TMP.
- the full length fusion gene was obtained from a third PCR reaction using the outside primers 1216-52 and 1830-55.
- the construct was delivered to the chromosome using a recombinant phage called AGebg-LacIQ#5 into F′tet/GM101. After recombination and resolution only the chromosomal insert described above remains in the cell. It was renamed F′tet/GM221.
- the F′tet episome was cured from the strain using acridine orange at a concentration of 25 ⁇ g/ml in LB. The cured strain was identified as tetracyline sensitive and was stored as GM221.
- This duplex was amplified in a PCR reaction using 1798-18 GCA GAA GAG CCT CTC CCT GTC TCC GGG TAA AGG TGG AGG TGG TGG TGG TGG AGG TAC TTA CTC T and 1798-19 CTA ATT GGA TCC ACG AGA TTA ACC ACC CTG CGG TTT GCA A
- the synthetic gene for the monomer was constructed from the 4 overlapping oligonucleotides 1798-4 and 1798-5 (above) and 1798-6 and 1798-7 (SEQ ID NOS: 400 and 401, respectively) shown below: 1798-6 GGC CCG CTG ACC TGG GTA TGT AAG CCA CAA GGG GGT GGG GGA GGC GGG GGG TAA TCT CGA G 1798-7 GAT CCT CGA GAT TAC CCC CCG CCT CCC CCA CCC CCT TGT GGC TTA CAT AC
- the final PCR gene product (the full length fusion gene) was digested with restriction endonucleases XbaI and BamHI, and then ligated into the vector pAMG21 and transformed into competent E. coli strain 2596 cells as described above. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #3688.
- the Fc portion of the molecule was generated in a PCR reaction with strain 3688 DNA using the primers 1798-23 and 1200-54 (shown above).
- EPO mimetic peptides were delivered to mice as a single bolus injection at a dose of 100 ⁇ g/kg.
- Fc-EMPs were delivered to mice in 7-day micro-osmotic pumps. The pumps were not replaced at the end of 7 days. Mice were bled until day 51 when HGB and HCT returned to baseline levels.
- oligonucleotide 2295-89 overlaps the glycine linker and Fc portion of the template by 22 nucleotides, with the PCR resulting in the two genes being fused together in the correct reading frame.
- FIGS. 20A and 20B The nucleotide and amino acid sequences (SEQ ID NOS: 1057 and 1058) of the fusion protein are shown in FIGS. 20A and 20B.
- the Fc portion of the molecule was generated in a PCR reaction with the pFc-A3 plasmid using the primers 2293-09 and 2293-10 as the sense and antisense primers (SEQ ID NOS. 1129 and 1130, respectively).
- the full length fusion gene was obtained from a third PCR reaction using the outside primers 2293-07 and 2293-10.
- the primer sequences are shown below: 2308-66 GAA TAA CAT ATG TGC ACC ACC CAC TGG GGT TTC ACC CTG TGC GGT GGA GGC GGT GGG GAC AAA 1200-54 GTT ATT GCT CAG CGG TGG CA
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- General Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Orthopedic Medicine & Surgery (AREA)
Abstract
The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising:
a) selecting at least one peptide that modulates the activity of a protein of interest; and
b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide.
Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.
Description
- Recombinant proteins are an emerging class of therapeutic agents. Such recombinant therapeutics have engendered advances in protein formulation and chemical modification. Such modifications can protect therapeutic proteins, primarily by blocking their exposure to proteolytic enzymes. Protein modifications may also increase the therapeutic protein's stability, circulation time, and biological activity. A review article describing protein modification and fusion proteins is Francis (1992),Focus on Growth Factors 3:4-10 (Mediscript, London), which is hereby incorporated by reference.
- One useful modification is combination with the “Fc” domain of an antibody. Antibodies comprise two functionally independent parts, a variable domain known as “Fab”, which binds antigen, and a constant domain known as “Fc”, which links to such effector functions as complement activation and attack by phagocytic cells. An Fc has a long serum half-life, whereas an Fab is short-lived. Capon et al. (1989),Nature 337: 525-31. When constructed together with a therapeutic protein, an Fc domain can provide longer half-life or incorporate such functions as Fc receptor binding, protein A binding, complement fixation and perhaps even placental transfer. Id. Table 1 summarizes use of Fc fusions known in the art.
TABLE 1 Fc fusion with therapeutic proteins Fusion Therapeutic Form of Fc partner implications Reference IgG1 N-terminus of Hodgkin's disease; U.S. Pat. No. CD30-L anaplastic lymphoma; T- 5,480,981 cell leukemia Murine Fcγ2a IL-10 anti-inflammatory; Zheng et al. (1995), J. Immunol. transplant rejection 154: 5590-600 IgG1 TNF receptor septic shock Fisher et al. (1996), N. Engl. J. Med. 334: 1697-1702; Van Zee, K. et al. (1996), J. Immunol. 156: 2221-30 IgG, IgA, TNF receptor inflammation, U.S. Pat. No. 5,808,029, IgM, or IgE autoimmune disorders issued Sep. 15, 1998 (excluding the first domain) IgG1 CD4 receptor AIDS Capon et al. (1989), Nature 337: 525-31 IgG1, N-terminus anti-cancer, antiviral Harvill et al. (1995), IgG3 of IL-2 Immunotech. 1: 95-105 IgG1 C-terminus of osteoarthritis; WO 97/23614, published OPG bone density Jul. 3, 1997 IgG1 N-terminus of anti-obesity PCT/US 97/23183, filed leptin Dec. 11, 1997 Human Ig CTLA-4 autoimmune disorders Linsley (1991), J. Exp. Cγ1 Med. 174: 561-9 - A much different approach to development of therapeutic agents is peptide library screening. The interaction of a protein ligand with its receptor often takes place at a relatively large interface. However, as demonstrated for human growth hormone and its receptor, only a few key residues at the interface contribute to most of the binding energy. Clackson et al. (1995),Science 267: 383-6. The bulk of the protein ligand merely displays the binding epitopes in the right topology or serves functions unrelated to binding. Thus, molecules of only “peptide” length (2 to 40 amino acids) can bind to the receptor protein of a given large protein ligand. Such peptides may mimic the bioactivity of the large protein ligand (“peptide agonists”) or, through competitive binding, inhibit the bioactivity of the large protein ligand (“peptide antagonists”).
- Phage display peptide libraries have emerged as a powerful method in identifying such peptide agonists and antagonists. See, for example, Scott et al. (1990),Science 249: 386; Devlin et al. (1990), Science 249: 404; U.S. Pat. No. 5,223,409, issued Jun. 29, 1993; U.S. Pat. No. 5,733,731, issued Mar. 31, 1998; U.S. Pat. No. 5,498,530, issued Mar. 12, 1996; U.S. Pat. No. 5,432,018, issued Jul. 11, 1995; U.S. Pat. No. 5,338,665, issued Aug. 16, 1994; U.S. Pat. No. 5,922,545, issued Jul. 13, 1999; WO 96/40987, published Dec. 19, 1996; and WO 98/15833, published Apr. 16, 1998 (each of which is incorporated by reference). In such libraries, random peptide sequences are displayed by fusion with coat proteins of filamentous phage. Typically, the displayed peptides are affinity-eluted against an antibody-immobilized extracellular domain of a receptor. The retained phages may be enriched by successive rounds of affinity purification and repropagation. The best binding peptides may be sequenced to identify key residues within one or more structurally related families of peptides. See, e.g., Cwirla et al. (1997), Science 276: 1696-9, in which two distinct families were identified. The peptide sequences may also suggest which residues may be safely replaced by alanine scanning or by mutagenesis at the DNA level. Mutagenesis libraries may be created and screened to further optimize the sequence of the best binders. Lowman (1997), Ann. Rev. Biophys. Biomol. Struct. 26: 401-24.
- Structural analysis of protein-protein interaction may also be used to suggest peptides that mimic the binding activity of large protein ligands. In such an analysis, the crystal structure may suggest the identity and relative orientation of critical residues of the large protein ligand, from which a peptide may be designed. See, e.g., Takasaki et al. (1997),Nature Biotech. 15: 1266-70. These analytical methods may also be used to investigate the interaction between a receptor protein and peptides selected by phage display, which may suggest further modification of the peptides to increase binding affinity.
- Other methods compete with phage display in peptide research. A peptide library can be fused to the carboxyl terminus of the lac repressor and expressed inE. coli. Another E. coli-based method allows display on the cell's outer membrane by fusion with a peptidoglycan-associated lipoprotein (PAL). Hereinafter, these and related methods are collectively referred to as “E. coli display.” In another method, translation of random RNA is halted prior to ribosome release, resulting in a library of polypeptides with their associated RNA still attached. Hereinafter, this and related methods are collectively referred to as “ribosome display.” Other methods employ chemical linkage of peptides to RNA; see, for example, Roberts & Szostak (1997), Proc. Natl. Acad. Sci. USA, 94:12297-303. Hereinafter, this and related methods are collectively referred to as “RNA-peptide screening.” Chemically derived peptide libraries have been developed in which peptides are immobilized on stable, non-biological materials, such as polyethylene rods or solvent-permeable resins. Another chemically derived peptide library uses photolithography to scan peptides immobilized on glass slides. Hereinafter, these and related methods are collectively referred to as “chemical-peptide screening.” Chemical-peptide screening may be advantageous in that it allows use of D-amino acids and other unnatural analogues, as well as non-peptide elements. Both biological and chemical methods are reviewed in Wells & Lowman (1992), Curr. Opin. Biotechnol. 3: 355-62.
- Conceptually, one may discover peptide mimetics of any protein using phage display and the other methods mentioned above. These methods have been used for epitope mapping, for identification of critical amino acids in protein-protein interactions, and as leads for the discovery of new therapeutic agents. E.g., Cortese et al. (1996),Curr. Opin. Biotech. 7: 616-21. Peptide libraries are now being used most often in immunological studies, such as epitope mapping. Kreeger (1996), The Scientist 10(13): 19-20.
- Of particular interest here is use of peptide libraries and other techniques in the discovery of pharmacologically active peptides. A number of such peptides identified in the art are summarized in Table 2. The peptides are described in the listed publications, each of which is hereby incorporated by reference. The pharmacologic activity of the peptides is described, and in many instances is followed by a shorthand term therefor in parentheses. Some of these peptides have been modified (e.g., to form C-terminally cross-linked dimers). Typically, peptide libraries were screened for binding to a receptor for a pharmacologically active protein (e.g., EPO receptor). In at least one instance (CTLA4), the peptide library was screened for binding to a monclonal antibody.
TABLE 2 Pharmacologically active peptides Binding partner/ Form of protein of Pharmacologic peptide interesta activity Reference intrapeptide EPO receptor EPO-mimetic Wrighton et al. (1996), disulfide- Science 273: 458-63; bonded U.S. Pat. No. 5,773,569, issued Jun. 30, 1998 to Wrighton et al. C-terminally EPO receptor EPO-mimetic Livnah et al. (1996), cross-linked Science 273: 464-71; dimer Wrighton et al. (1997), Nature Biotechnology 15: 1261-5; International patent application WO 96/40772, published Dec. 19, 1996 linear EPO receptor EPO-mimetic Naranda et al. (1999), Proc. Natl. Acad. Sci. USA, 96: 7569-74 linear c-Mpl TPO-mimetic Cwirla et al. (1997) Science 276: 1696-9; U.S. Pat. No. 5,869,451, issued Feb. 9, 1999; U.S. Pat. No. 5,932,946, issued Aug. 3, 1999 C-terminally c-Mpl TPO-mimetic Cwirla et al. (1997), cross-linked Science 276: 1696-9 dimer disulfide- stimulation of Paukovits et al. (1984), linked dimer hematopoiesis Hoppe-Seylers Z. (“G-CSF-mimetic”) Physiol. Chem. 365: 303-11; Laerum et al. (1988), Exp. Hemat. 16: 274-80 alkylene- G-CSF-mimetic Bhatnagar et al. (1996), linked dimer J. Med. Chem. 39: 3814-9; Cuthbertson et al. (1997), J. Med. Chem. 40: 2876-82; King et al. (1991), Exp. Hematol. 19: 481; King et al. (1995), Blood 86 (Suppl. 1): 309a linear IL-1 receptor inflammatory and U.S Pat. No. 5,608,035; autoimmune diseases U.S. Pat. No. 5,786,331; (“IL-1 antagonist” or U.S. Pat. No. 5,880,096; “IL-1ra-mimetic”) Yanofsky et al. (1996), Proc. Natl. Acad. Sci. 93: 7381-6; Akeson et al. (1996), J. Biol. Chem. 271: 30517-23; Wiekzorek et al. (1997), Pol. J. Pharmacol. 49: 107-17; Yanofsky (1996), PNAs, 93: 7381-7386. linear Facteur stimulation of Inagaki-Ohara et al. thymique lymphocytes (1996), Cellular Immunol. serique (FTS) (“FTS-mimetic”) 171: 30-40; Yoshida (1984), Int. J. Immunopharmacol, 6: 141-6. intrapeptide CTLA4 MAb CTLA4-mimetic Fukumoto et al. (1998), disulfide Nature Biotech. 16: 267-70 bonded exocyclic TNF-α receptor TNF-α antagonist Takasaki et al. (1997), Nature Biotech. 15: 1266-70; WO 98/53842, published Dec. 3, 1998 linear TNF-α receptor TNF-α antagonist Chirinos-Rojas ( ), J. Imm., 5621-5626. intrapeptide C3b inhibition of complement Sahu et al. (1996), J. Immunol. disulfide activation; autoimmune 157: 884-91; bonded diseases Morikis et al. (1998), (“C3b-antagonist”) Protein Sci. 7: 619-27 linear vinculin cell adhesion processes - Adey et al. (1997), cell growth, differentiation, Biochem. J. 324: 523-8 wound healing, tumor metastasis (“vinculin binding”) linear C4 binding anti-thrombotic Linse et al. (1997), J. Biol. Chem. protein (C4BP) 272: 14658-65 linear urokinase processes associated with Goodson et al. (1994), receptor urokinase interaction with Proc. Natl. Acad. Sci. 91: its receptor (e.g., 7129-33; International angiogenesis, tumor cell application WO invasion and metastasis); 97/35969, published (“UKR antagonist”) Oct. 2, 1997 linear Mdm2, Hdm2 Inhibition of inactivation of Picksley et al. (1994), p53 mediated by Mdm2 or Oncogene 9: 2523-9; hdm2; anti-tumor Bottger et al. (1997) J. Mol. Biol. (“Mdm/hdm antagonist”) 269: 744-56; Bottger et al. (1996), Oncogene 13: 2141-7 linear p21WAF1 anti-tumor by mimicking Ball et al. (1997), Curr. the activity of p21WAF1 Biol. 7: 71-80 linear farnesyl anti-cancer by preventing Gibbs et al. (1994), Cell transferase activation of ras oncogene 77: 175-178 linear Ras effector anti-cancer by inhibiting Moodie et al. (1994), domain biological function of the Trends Genet 10: 44-48 ras oncogene Rodriguez et al. (1994), Nature 370: 527-532 linear SH2/SH3 anti-cancer by inhibiting Pawson et al (1993), domains tumor growth with Curr. Biol. 3: 434-432 activated tyrosine kinases Yu et al. (1994), Cell 76: 933-945 linear p16INK4 anti-cancer by mimicking F$$hraeus et al. (1996), activity of p16; e.g., Curr. Biol. 6: 84-91 inhibiting cyclin D-Cdk complex (“p16-mimetic”) linear Src, Lyn inhibition of Mast cell Stauffer et al. (1997), activation, IgE-related Biochem. 36: 9388-94 conditions, type I hypersensitivity (“Mast cell antagonist”) linear Mast cell treatment of inflammatory International application protease disorders mediated by WO 98/33812, published release of tryptase-6 Aug. 6, 1998 (“Mast cell protease inhibitors”) linear SH3 domains treatment of SH3- Rickles et al. (1994), mediated disease states EMBO J. 13: 5598-5604; (“SH3 antagonist”) Sparks et al. (1994), J. Biol. Chem. 269: 23853-6; Sparks et al. (1996), Proc. Natl. Acad. Sci. 93: 1540-4 linear HBV core treatment of HBV viral Dyson & Muray (1995), antigen (HBcAg) infections (“anti-HBV”) Proc. Natl. Acad. Sci. 92: 2194-8 linear selectins neutrophil adhesion; Martens et al. (1995), J. Biol. Chem. inflammatory diseases 270: 21129-36; (“selectin antagonist”) European patent application EP 0 714 912, published Jun. 5, 1996 linear, calmodulin calmodulin antagonist Pierce et al. (1995), cyclized Molec. Diversity 1: 259-65 Dedman et al. (1993), J. Biol. Chem. 268: 23025-30; Adey & Kay (1996), Gene 169: 133-4 linear, integrins tumor-homing; treatment International applications cyclized- for conditions related to WO 95/14714, published integrin-mediated cellular Jun. 1, 1995; WO events, including platelet 97/08203, published aggregation, thrombosis, Mar. 6, 1997; WO wound healing, 98/10795, published osteoporosis, tissue Mar. 19, 1998; WO repair, angiogenesis (e.g., 99/24462, published May for treatment of cancer), 20, 1999; Kraft et al. and tumor invasion (1999), J. Biol. Chem. (“integrin-binding”) 274: 1979-1985 cyclic, linear fibronectin and treatment of inflammatory WO 98/09985, extracellular and autoimmune published Mar. 12, 1998 matrix conditions components of T cells and macrophages linear somatostatin treatment or prevention of European patent and cortistatin hormone-producing application 0 911 393,tumors, acromegaly, published Apr. 8, 1999 giantism, dementia, gastric ulcer, tumor growth, inhibition of hormone secretion, modulation of sleep or neural activity linear bacterial antibiotic; septic shock; U.S. Pat. No. 5,877,151, lipopolysaccharide disorders modulatable by issued Mar. 2, 1999 CAP37 linear or pardaxin, antipathogenic WO 97/31019, published cyclic, mellitin Aug. 28, 1997 including D- amino acids linear, cyclic VIP impotence, WO 97/40070, published neurodegenerative Oct. 30, 1997 disorders linear CTLs cancer EP 0 770 624, published May 2, 1997 linear THF-gamma2 Burnstein (1988), Biochem., 27: 4066-71. linear Amylin Cooper (1987), Proc. Natl. Acad. Sci., 84: 8628-32. linear Adrenomedullin Kitamura (1993), BBRC, 192: 553-60. cyclic, linear VEGF anti-angiogenic; cancer, Fairbrother (1998), rheumatoid arthritis, Biochem., 37: 17754-17764. diabetic retinopathy, psoriasis (“VEGF antagonist”) cyclic MMP inflammation and Koivunen (1999), Nature autoimmune disorders; Biotech., 17: 768-774. tumor growth (“MMP inhibitor”) HGH fragment U.S. Pat. No. 5,869,452 Echistatin inhibition of platelet Gan (1988), J. Biol. Chem., aggregation 263: 19827-32. linear SLE SLE WO 96/30057, published autoantibody Oct. 3, 1996 GD1alpha suppression of tumor Ishikawa et al. (1998), metastasis FEBS Lett. 441 (1): 20-4 antiphospholipid endothelial cell activation, Blank et al. (1999), Proc. beta-2- antiphospholipid Natl. Acad. Sci. USA 96: glycoprotein-i syndrome (APS), 5164-8 (β2GPI) thromboembolic antibodies phenomena, thrombocytopenia, and recurrent fetal loss linear T Cell Receptor diabetes WO 96/11214, published beta chain Apr. 18, 1996 - Peptides identified by peptide library screening have been regarded as “leads” in development of therapeutic agents rather than as therapeutic agents themselves. Like other proteins and peptides, they would be rapidly removed in vivo either by renal filtration, cellular clearance mechanisms in the reticuloendothelial system, or proteolytic degradation. Francis (1992),Focus on Growth Factors 3: 4-11. As a result, the art presently uses the identified peptides to validate drug targets or as scaffolds for design of organic compounds that might not have been as easily or as quickly identified through chemical library screening. Lowman (1997), Ann. Rev. Biophys. Biomol. Struct. 26: 401-24; Kay et al. (1998), Drug Disc. Today 3: 370-8. The art would benefit from a process by which such peptides could more readily yield therapeutic agents.
- The present invention concerns a process by which the in vivo half-life of one or more biologically active peptides is increased by fusion with a vehicle. In this invention, pharmacologically active compounds are prepared by a process comprising:
- a) selecting at least one peptide that modulates the activity of a protein of interest; and
- b) preparing a pharmacologic agent comprising at least one vehicle covalently linked to at least one amino acid sequence of the selected peptide.
- The preferred vehicle is an Fc domain. The peptides screened in step (a) are preferably expressed in a phage display library. The vehicle and the peptide may be linked through the N- or C-terminus of the peptide or the vehicle, as described further below. Derivatives of the above compounds (described below) are also encompassed by this invention.
- The compounds of this invention may be prepared by standard synthetic methods, recombinant DNA techniques, or any other methods of preparing peptides and fusion proteins. Compounds of this invention that encompass non-peptide portions may be synthesized by standard organic chemistry reactions, in addition to standard peptide chemistry reactions when applicable.
- The primary use contemplated is as therapeutic or prophylactic agents. The vehicle-linked peptide may have activity comparable to—or even greater than—the natural ligand mimicked by the peptide. In addition, certain natural ligand-based therapeutic agents might induce antibodies against the patient's own endogenous ligand; the vehicle-linked peptide avoids this pitfall by having little or typically no sequence identity with the natural ligand.
- Although mostly contemplated as therapeutic agents, compounds of this invention may also be useful in screening for such agents. For example, one could use an Fc-peptide (e.g., Fc-SH2 domain peptide) in an assay employing anti-Fc coated plates. The vehicle, especially Fc, may make insoluble peptides soluble and thus useful in a number of assays.
- The compounds of this invention may be used for therapeutic or prophylactic purposes by formulating them with appropriate pharmaceutical carrier materials and administering an effective amount to a patient, such as a human (or other mammal) in need thereof. Other related aspects are also included in the instant invention.
- Numerous additional aspects and advantages of the present invention will become apparent upon consideration of the figures and detailed description of the invention.
- FIG. 1 shows a schematic representation of an exemplary process of the invention. In this preferred process, the vehicle is an Fc domain, which is linked to the peptide covalently by expression from a DNA construct encoding both the Fc domain and the peptide. As noted in FIG. 1, the Fc domains spontaneously form a dimer in this process.
- FIG. 2 shows exemplary Fc dimers that may be derived from an IgG1 antibody. “Fc” in the figure represents any of the Fc variants within the meaning of “Fc domain” herein. “X1” and “X2” represent peptides or linker-peptide combinations as defined hereinafter. The specific dimers are as follows:
- A, D: Single disulfide-bonded dimers. IgG1 antibodies typically have two disulfide bonds at the hinge region between the constant and variable domains. The Fc domain in FIGS. 2A and 2D may be formed by truncation between the two disulfide bond sites or by substitution of a cysteinyl residue with an unreactive residue (e.g., alanyl). In FIG. 2A, the Fc domain is linked at the amino terminus of the peptides; in2D, at the carboxyl terminus.
- B, E: Doubly disulfide-bonded dimers. This Fc domain may be formed by truncation of the parent antibody to retain both cysteinyl residues in the Fc domain chains or by expression from a construct including a sequence encoding such an Fc domain. In FIG. 2B, the Fc domain is linked at the amino terminus of the peptides; in2E, at the carboxyl terminus.
- C, F: Noncovalent dimers. This Fc domain may be formed by elimination of the cysteinyl residues by either truncation or substitution. One may desire to eliminate the cysteinyl residues to avoid impurities formed by reaction of the cysteinyl residue with cysteinyl residues of other proteins present in the host cell. The noncovalent bonding or the Fc domains is sufficient to hold together the dimer.
- Other dimers may be formed by using Fc domains derived from different types of antibodies (e.g., IgG2, IgM).
- FIG. 3 shows the structure of preferred compounds of the invention that feature tandem repeats of the pharmacologically active peptide. FIG. 3A shows a single chain molecule and may also represent the DNA construct for the molecule. FIG. 3B shows a dimer in which the linker-peptide portion is present on only one chain of the dimer. FIG. 3C shows a dimer having the peptide portion on both chains. The dimer of FIG. 3C will form spontaneously in certain host cells upon expression of a DNA construct encoding the single chain shown in FIG. 3A. In other host cells, the cells could be placed in conditions favoring formation of dimers or the dimers can be formed in vitro.
- FIG. 4 shows exemplary nucleic acid and amino acid sequences (SEQ ID NOS: 1 and 2, respectively) of human IgG1 Fc that may be used in this invention.
- FIG. 5 shows a synthetic scheme for the preparation of PEGylated peptide 19 (SEQ ID NO: 3).
- FIG. 6 shows a synthetic scheme for the preparation of PEGylated peptide 20 (SEQ ID NO: 4).
- FIG. 7 shows the nucleotide and amino acid sequences (SEQ ID NOS: 5 and 6, respectively) of the molecule identified as “Fc-TMP” in Example 2 hereinafter.
- FIG. 8 shows the nucleotide and amino acid sequences (SEQ. ID. NOS: 7 and 8, respectively) of the molecule identified as “Fc-TMP-TMP” in Example 2 hereinafter.
- FIG. 9 shows the nucleotide and amino acid sequences (SEQ. ID. NOS: 9 and 10, respectively) of the molecule identified as “TMP-TMP-Fc” in Example 2 hereinafter.
- FIG. 10 shows the nucleotide and amino acid sequences (SEQ. ID. NOS: 11 and 12, respectively) of the molecule identified as “TMP-Fc” in Example 2 hereinafter.
- FIG. 11 shows the number of platelets generated in vivo in normal female BDF1 mice treated with one 100 μg/kg bolus injection of various compounds, with the terms defined as follows.
- PEG-MGDF: 20 kD average molecular weight PEG attached by reductive amination to the N-terminal amino group of amino acids 1-163 of native human TPO, which is expressed inE. coli (so that it is not glycosylated);
- TMP: the TPO-mimetic peptide having the amino acid sequence IEGPTLRQWLAARA (SEQ ID NO: 13); TMP-TMP: the TPO-mimetic peptide having the amino acid sequence IEGPTLRQWLAARA-GGGGGGGG-IEGPTLRQWLAARA (SEQ ID NO: 14);
- PEG-TMP-TMP: the peptide of SEQ ID NO: 14, wherein the PEG group is a 5 kD average molecular weight PEG attached as shown in FIG. 6;
- Fc-TMP-TMP: the compound of SEQ ID NO: 8 (FIG. 8) dimerized with an identical second monomer (i.e.,
Cys residues - TMP-TMP-Fc is the compound of SEQ ID NO: 10 (FIG. 9) dimerized in the same way as TMP-TMP-Fc except that the Fc domain is attached at the C-terminal end rather than the N-terminal end of the TMP-TMP peptide.
- FIG. 12 shows the number of platelets generated in vivo in normal BDF1 mice treated with various compounds delivered via implanted osmotic pumps over a 7-day period. The compounds are as defined for FIG. 7.
- FIG. 13 shows the nucleotide and amino acid sequences (SEQ. ID. NOS: 15 and 16, respectively) of the molecule identified as “Fc-EMP” in Example 3 hereinafter.
- FIG. 14 shows the nucleotide and amino acid sequences (SEQ ID NOS: 17 and 18, respectively) of the molecule identified as “EMP-Fc” in Example 3 hereinafter.
- FIG. 15 shows the nucleotide and amino acid sequences (SEQ ID NOS:19 and 20, respectively) of the molecule identified as “EMP-EMP-Fc” in Example 3 hereinafter.
- FIG. 16 shows the nucleotide and amino acid sequences (SEQ ID NOS: 21 and 22, respectively) of the molecule identified as “Fc-EMP-EMP” in Example 3 hereinafter.
- FIGS. 17A and 17B show the DNA sequence (SEQ ID NO: 23) inserted into pCFM1656 between the unique AatII (position #4364 in pCFM1656) and SacII (position #4585 in pCFM1656) restriction sites to form expression plasmid pAMG21 (ATCC accession no. 98113).
- FIG. 18A shows the hemoglobin, red blood cells, and hematocrit generated in vivo in normal female BDF1 mice treated with one 100 μg/kg bolus injection of various compounds. FIG. 18B shows the same results with mice treated with 100 μg/kg per day delivered the same dose by 7-day micro-osmotic pump with the EMPs delivered at 100 μg/kg, rhEPO at 30 U/mouse. (In both experiments, neutrophils, lymphocytes, and platelets were unaffected.) In these figures, the terms are defined as follows.
- Fc-EMP: the compound of SEQ ID NO: 16 (FIG. 13) dimerized with an identical second monomer (i.e.,
Cys residues - EMP-Fc: the compound of SEQ ID NO: 18 (FIG. 14) dimerized in the same way as Fc-EMP except that the Fc domain is attached at the C-terminal end rather than the N-terminal end of the EMP peptide.
- “EMP-EMP-Fc” refers to a tandem repeat of the same peptide (SEQ ID NO: 20) attached to the same Fc domain by the carboxyl terminus of the peptides. “Fc-EMP-EMP” refers to the same tandem repeat of the peptide but with the same Fc domain attached at the amino terminus of the tandem repeat. All molecules are expressed inE. coli and so are not glycosylated.
- FIGS. 19A and 19B show the nucleotide and amino acid sequences (SEQ ID NOS: 1055 and 1056) of the Fc-TNF-α inhibitor fusion molecule described in Example 4 hereinafter.
- FIGS. 20A and 20B show the nucleotide and amino acid sequences (SEQ ID NOS: 1057 and 1058) of the TNF-α inhibitor-Fc fusion molecule described in Example 4 hereinafter.
- FIGS. 21A and 21B show the nucleotide and amino acid sequences (SEQ ID NOS: 1059 and 1060) of the Fc-IL-1 antagonist fusion molecule described in Example 5 hereinafter.
- FIGS. 22A and 22B show the nucleotide and amino acid sequences (SEQ ID NOS: 1061 and 1062) of the IL-1 antagonist-Fc fusion molecule described in Example 5 hereinafter.
- FIGS. 23A, 23B, and23C show the nucleotide and amino acid sequences (SEQ ID NOS: 1063 and 1064) of the Fc-VEGF antagonist fusion molecule described in Example 6 hereinafter.
- FIGS. 24A and 24B show the nucleotide and amino acid sequences (SEQ ID NOS: 1065 and 1066) of the VEGF antagonist-Fc fusion molecule described in Example 6 hereinafter.
- FIGS. 25A and 25B show the nucleotide and amino acid sequences (SEQ ID NOS: 1067 and 1068) of the Fc-MMP inhibitor fusion molecule described in Example 7 hereinafter.
- FIGS. 26A and 26B show the nucleotide and amino acid sequences (SEQ ID NOS: 1069 and 1070) of the MMP inhibitor-Fc fusion molecule described in Example 7 hereinafter.
- Definition of Terms
- The terms used throughout this specification are defined as follows, unless otherwise limited in specific instances.
- The term “comprising” means that a compound may include additional amino acids on either or both of the N- or C-termini of the given sequence. Of course, these additional amino acids should not significantly interfere with the activity of the compound.
- The term “vehicle” refers to a molecule that prevents degradation and/or increases half-life, reduces toxicity, reduces immunogenicity, or increases biological activity of a therapeutic protein. Exemplary vehicles include an Fc domain (which is preferred) as well as a linear polymer (e.g., polyethylene glycol (PEG), polylysine, dextran, etc.); a branched-chain polymer (see, for example, U.S. Pat. No. 4,289,872 to Denkenwalter et al., issued Sep. 15, 1981; U.S. Pat. No. 5,229,490 to Tam, issued Jul. 20, 1993; WO 93/21259 by Frechet et al., published Oct. 28, 1993); a lipid; a cholesterol group (such as a steroid); a carbohydrate or oligosaccharide; or any natural or synthetic protein, polypeptide or peptide that binds to a salvage receptor. Vehicles are further described hereinafter.
- The term “native Fc” refers to molecule or sequence comprising the sequence of a non-antigen-binding fragment resulting from digestion of whole antibody, whether in monomeric or multimeric form. The original immunoglobulin source of the native Fc is preferably of human origin and may be any of the immunoglobulins, although IgG1 and IgG2 are preferred. Native Fc's are made up of monomeric polypeptides that may be linked into dimeric or multimeric forms by covalent (i.e., disulfide bonds) and non-covalent association. The number of intermolecular disulfide bonds between monomeric subunits of native Fc molecules ranges from 1 to 4 depending on class (e.g., IgG, IgA, IgE) or subclass (e.g., IgG1, IgG2, IgG3, IgA1, IgGA2). One example of a native Fc is a disulfide-bonded dimer resulting from papain digestion of an IgG (see Ellison et al. (1982),Nucleic Acids Res. 10: 4071-9). The term “native Fc” as used herein is generic to the monomeric, dimeric, and multimeric forms.
- The term “Fc variant” refers to a molecule or sequence that is modified from a native Fc but still comprises a binding site for the salvage receptor, FcRn. International applications WO 97/34631 (published Sep. 25, 1997) and WO 96/32478 describe exemplary Fc variants, as well as interaction with the salvage receptor, and are hereby incorporated by reference. Thus, the term “Fc variant” comprises a molecule or sequence that is humanized from a non-human native Fc. Furthermore, a native Fc comprises sites that may be removed because they provide structural features or biological activity that are not required for the fusion molecules of the present invention. Thus, the term “Fc variant” comprises a molecule or sequence that lacks one or more native Fc sites or residues that affect or are involved in (1) disulfide bond formation, (2) incompatibility with a selected host cell (3) N-terminal heterogeneity upon expression in a selected host cell, (4) glycosylation, (5) interaction with complement, (6) binding to an Fc receptor other than a salvage receptor, or (7) antibody-dependent cellular cytotoxicity (ADCC). Fc variants are described in further detail hereinafter.
- The term “Fc domain” encompasses native Fc and Fc variant molecules and sequences as defined above. As with Fc variants and native Fc's, the term “Fc domain” includes molecules in monomeric or multimeric form, whether digested from whole antibody or produced by other means.
- The term “multimer” as applied to Fc domains or molecules comprising Fc domains refers to molecules having two or more polypeptide chains associated covalently, noncovalently, or by both covalent and non-covalent interactions. IgG molecules typically form dimers; IgM, pentamers; IgD, dimers; and IgA, monomers, dimers, trimers, or tetramers. Multimers may be formed by exploiting the sequence and resulting activity of the native Ig source of the Fc or by derivatizing (as defined below) such a native Fc.
- The term “dimer” as applied to Fc domains or molecules comprising Fc domains refers to molecules having two polypeptide chains associated covalently or non-covalently. Thus, exemplary dimers within the scope of this invention are as shown in FIG. 2.
- The terms “derivatizing” and “derivative” or “derivatized” comprise processes and resulting compounds respectively in which (1) the compound has a cyclic portion; for example, cross-linking between cysteinyl residues within the compound; (2) the compound is cross-linked or has a cross-linking site; for example, the compound has a cysteinyl residue and thus forms cross-linked dimers in culture or in vivo; (3) one or more peptidyl linkage is replaced by a non-peptidyl linkage; (4) the N-terminus is replaced by —NRR1, NRC(O)R1, —NRC(O)OR1, —NRS(O)2R1, —NHC(O)NHR, a succinimide group, or substituted or unsubstituted benzyloxycarbonyl-NH—, wherein R and R1 and the ring substituents are as defined hereinafter; (5) the C-terminus is replaced by —C(O)R2 or —NR3R4 wherein R2, R3 and R4 are as defined hereinafter; and (6) compounds in which individual amino acid moieties are modified through treatment with agents capable of reacting with selected side chains or terminal residues. Derivatives are further described hereinafter.
- The term “peptide” refers to molecules of 2 to 40 amino acids, with molecules of 3 to 20 amino acids preferred and those of 6 to 15 amino acids most preferred. Exemplary peptides may be randomly generated by any of the methods cited above, carried in a peptide library (e.g., a phage display library), or derived by digestion of proteins.
- The term “randomized” as used to refer to peptide sequences refers to fully random sequences (e.g., selected by phage display methods) and sequences in which one or more residues of a naturally occurring molecule is replaced by an amino acid residue not appearing in that position in the naturally occurring molecule. Exemplary methods for identifying peptide sequences include phage display,E. coli display, ribosome display, RNA-peptide screening, chemical screening, and the like.
- The term “pharmacologically active” means that a substance so described is determined to have activity that affects a medical parameter (e.g., blood pressure, blood cell count, cholesterol level) or disease state (e.g., cancer, autoimmune disorders). Thus, pharmacologically active peptides comprise agonistic or mimetic and antagonistic peptides as defined below.
- The terms “-mimetic peptide” and “-agonist peptide” refer to a peptide having biological activity comparable to a protein (e.g., EPO, TPO, G-CSF) that interacts with a protein of interest. These terms further include peptides that indirectly mimic the activity of a protein of interest, such as by potentiating the effects of the natural ligand of the protein of interest; see, for example, the G-CSF-mimetic peptides listed in Tables 2 and 7. Thus, the term “EPO-mimetic peptide” comprises any peptides that can be identified or derived as described in Wrighton et al. (1996),Science 273: 458-63, Naranda et al. (1999), Proc. Natl. Acad. Sci. USA 96: 7569-74, or any other reference in Table 2 identified as having EPO-mimetic subject matter. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- The term “TPO-mimetic peptide” comprises peptides that can be identified or derived as described in Cwirla et al. (1997),Science 276: 1696-9, U.S. Pat. Nos. 5,869,451 and 5,932,946 and any other reference in Table 2 identifed as having TPO-mimetic subject matter, as well as the U.S. patent application, “Thrombopoietic Compounds,” filed on even date herewith and hereby incorporated by reference. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- The term “G-CSF-mimetic peptide” comprises any peptides that can be identified or described in Paukovits et al. (1984),Hoppe-Seylers Z. Physiol. Chem. 365: 303-11 or any of the references in Table 2 identified as having G-CSF-mimetic subject matter. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- The term “CTLA4-mimetic peptide” comprises any peptides that can be identified or derived as described in Fukumoto et al. (1998),Nature Biotech. 16: 267-70. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- The term “-antagonist peptide” or “inhibitor peptide” refers to a peptide that blocks or in some way interferes with the biological activity of the associated protein of interest, or has biological activity comparable to a known antagonist or inhibitor of the associated protein of interest. Thus, the term “TNF-antagonist peptide” comprises peptides that can be identified or derived as described in Takasaki et al. (1997),Nature Biotech. 15: 1266-70 or any of the references in Table 2 identified as having TNF-antagonistic subject matter. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- The terms “IL-1 antagonist” and “IL-1ra-mimetic peptide” comprises peptides that inhibit or down-regulate activation of the IL-1 receptor by IL-1. IL-1 receptor activation results from formation of a complex among IL-1, IL-1 receptor, and IL-1 receptor accessory protein. IL-1 antagonist or IL-1ra-mimetic peptides bind to IL-1, IL-1 receptor, or IL-1 receptor accessory protein and obstruct complex formation among any two or three components of the complex. Exemplary IL-1 antagonist or IL-1ra-mimetic peptides can be identified or derived as described in U.S. Pat. Nos. 5,608,035, 5,786,331, 5,880,096, or any of the references in Table 2 identified as having IL-1ra-mimetic or IL-1 antagonistic subject matter. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- The term “VEGF-antagonist peptide” comprises peptides that can be identified or derived as described in Fairbrother (1998),Biochem. 37: 17754-64, and in any of the references in Table 2 identified as having VEGF-antagonistic subject matter. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- The term “MMP inhibitor peptide” comprises peptides that can be identified or derived as described in Koivunen (1999),Nature Biotech. 17: 768-74 and in any of the references in Table 2 identified as having MMP inhibitory subject matter. Those of ordinary skill in the art appreciate that each of these references enables one to select different peptides than actually disclosed therein by following the disclosed procedures with different peptide libraries.
- Additionally, physiologically acceptable salts of the compounds of this invention are also encompassed herein. By “physiologically acceptable salts” is meant any salts that are known or later discovered to be pharmaceutically acceptable. Some specific examples are: acetate; trifluoroacetate; hydrohalides, such as hydrochloride and hydrobromide; sulfate; citrate; tartrate; glycolate; and oxalate.
- Structure of Compounds
- In General. In the compositions of matter prepared in accordance with this invention, the peptide may be attached to the vehicle through the peptide's N-terminus or C-terminus. Thus, the vehicle-peptide molecules of this invention may be described by the following formula I:
- (X1)a-F1-(X2)b I
- wherein:
- F1 is a vehicle (preferably an Fc domain);
- X1 and X2 are each independently selected from -(L1)c-P1, -(L1)c-P1-(L1)d-P2, -(L1)c-P1-(L2)d-P2-(L3)e-P3, and -(L1)c-P1-(L2)d-P2-(L3)e-P3-(L4)f-P4
- P1, P2, P3, and P4 are each independently sequences of pharmacologically active peptides;
- L1, L2, L3, and L4 are each independently linkers; and
- a, b, c, d, e, and f are each independently 0 or 1, provided that at least one of a and b is 1.
- Thus, compound I comprises preferred compounds of the formulae
- X1-F1 II
- and multimers thereof wherein F1 is an Fc domain and is attached at the C-terminus of X1;
- F1-X2 III
- and multimers thereof wherein F1 is an Fc domain and is attached at the N-terminus of X2;
- F1-(L1)c-P1 IV
- and multimers thereof wherein F1 is an Fc domain and is attached at the N-terminus of -(L1)c-P1; and
- F-(L1)c-P1-(L2)d-P2 V
- and multimers thereof wherein F1 is an Fc domain and is attached at the N-terminus of -L1-P1-L2-P2.
- Peptides. Any number of peptides may be used in conjunction with the present invention. Of particular interest are peptides that mimic the activity of EPO, TPO, growth hormone, G-CSF, GM-CSF, IL-1ra, leptin, CTLA4, TRAIL, TGF-α, and TGF-β. Peptide antagonists are also of interest, particularly those antagonistic to the activity of TNF, leptin, any of the interleukins (IL-1, 2, 3, . . . ), and proteins involved in complement activation (e.g., C3b). Targeting peptides are also of interest, including tumor-homing peptides, membrane-transporting peptides, and the like. All of these classes of peptides may be discovered by methods described in the references cited in this specification and other references.
- Phage display, in particular, is useful in generating peptides for use in the present invention. It has been stated that affinity selection from libraries of random peptides can be used to identify peptide ligands for any site of any gene product. Dedman et al. (1993),J. Biol. Chem. 268: 23025-30. Phage display is particularly well suited for identifying peptides that bind to such proteins of interest as cell surface receptors or any proteins having linear epitopes. Wilson et al. (1998), Can. T. Microbiol. 44: 313-29; Kay et al. (1998), Drug Disc. Today 3: 370-8. Such proteins are extensively reviewed in Herz et al. (1997), T. Receptor & Signal Transduction Res. 17(5): 671-776, which is hereby incorporated by reference. Such proteins of interest are preferred for use in this invention.
- A particularly preferred group of peptides are those that bind to cytokine receptors. Cytokines have recently been classified according to their receptor code. See Inglot (1997),Archivum Immunologiae et Therapiae Experimentalis 45: 353-7, which is hereby incorporated by reference. Among these receptors, most preferred are the CKRs (family I in Table 3). The receptor classification appears in Table 3.
TABLE 3 Cytokine Receptors Classified by Receptor Code Cytokines (ligands) Receptor Type family subfamily family subfamily I. Hematopoietic 1. IL-2, IL-4, IL-7, I. Cytokine R 1. shared γCr cytokines IL-9, IL-13, IL- (CKR) 15 2. IL-3, IL-5, GM- 2. shared GP CSF 140 βR 3. IL-6, IL-11, IL- 3. 3.shared 12, LIF, OSM, RP 130 CNTF, leptin (OB) 4. G-CSF, EPO, 4. “single TPO, PRL, GH chain” R 5. IL-17, HVS-IL- 5. other R c17 II. IL-10 ligands IL-10, BCRF-1, II. IL-10 R HSV-IL-10 III. Interferons 1. IFN-αl, α2, α4, III. Interferon R 1. IFNAR m, t, IFN- β d2. IFN- γ 2. IFNGR IV. IL-1 ligands 1. IL-1α, IL-1β, IL- IV. IL-1R 1Ra V. TNF ligands 1. TNF-α, TNF-β V. NGF/TNF Re (LT), FAS1, CD40 L, CD30L, CD27 L VI. Chemokines 1. α chemokines: VI. Chemokine R 1. CXCR IL-8, GRO α, β, γ, IF-10, PF-4, SDF-1 2. β chemokines: 2. CCR MIP1α, MIP1β, MCP-1, 2, 3, 4, RANTES, eotaxin 3. γ chemokines: 3. CR lymphotactin 4. DARCf VII. Growth 1.1 SCF, M-CSF, VII. RKF 1. TK factors PDGF-AA, AB, sub-family BB, FLT-3L, 1.1 IgTK VEGF, SSV- III R PDGF 1.2 FGFα, FGFβ 1.2 IgTK 1.3 EGF, TGF-α, IV R VV-F19 (EGF- 1.3 Cysteine- like) rich TK-I 1.4 IGF-I, IGF-II, 1.4 Cysteine Insulin rich TK-II 1.5 NGF, BDNF, 1.5 Cysteine NT-3, NT-4g knot TK V 2. TGF-β1, β2, β3 2. STK subfamilyh - Exemplary peptides for this invention appear in Tables 4 through 20 below. These peptides may be prepared by methods disclosed in the art. Single letter amino acid abbreviations are used. The X in these sequences (and throughout this specification, unless specified otherwise in a particular instance) means that any of the 20 naturally occurring amino acid residues may be present. Any of these peptides may be linked in tandem (i.e., sequentially), with or without linkers, and a few tandem-linked examples are provided in the table. Linkers are listed as “A” and may be any of the linkers described herein. Tandem repeats and linkers are shown separated by dashes for clarity. Any peptide containing a cysteinyl residue may be cross-linked with another Cys-containing peptide, either or both of which may be linked to a vehicle. A few cross-linked examples are provided in the table. Any peptide having more than one Cys residue may form an intrapeptide disulfide bond, as well; see, for example, EPO-mimetic peptides in Table 5. A few examples of intrapeptide disulfide-bonded peptides are specified in the table. Any of these peptides may be derivatized as described herein, and a few derivatized examples are provided in the table. Derivatized peptides in the tables are exemplary rather than limiting, as the associated underivatized peptides may be employed in this invention, as well. For derivatives in which the carboxyl terminus may be capped with an amino group, the capping amino group is shown as —NH2. For derivatives in which amino acid residues are substituted by moieties other than amino acid residues, the substitutions are denoted by σ, which signifies any of the moieties described in Bhatnagar et al. (1996), J. Med. Chem. 39: 3814-9 and Cuthbertson et al. (1997), T. Med. Chem. 40: 2876-82, which are incorporated by reference. The J substituent and the Z substituents (Z5, Z6, . . . Z40) are as defined in U.S. Pat. Nos. 5,608,035, 5,786,331, and 5,880,096, which are incorporated by reference. For the EPO-mimetic sequences (Table 5), the substituents X2 through X11 and the integer “n” are as defined in WO 96/40772, which is incorporated by reference. The substituents “Ψ,” “Θ,” and “+” are as defined in Sparks et al. (1996), Proc. Natl. Acad. Sci. 93: 1540-4, which is hereby incorporated by reference. X4, X5, X6, and X7 are as defined in U.S. Pat. No. 5,773,569, which is hereby incorporated by reference, except that: for integrin-binding peptides, X1, X2, X3, X4, X5, X6, X7, and X8 are as defined in International applications WO 95/14714, published Jun. 1, 1995 and WO 97/08203, published Mar. 6, 1997, which are also incorporated by reference; and for VIP-mimetic peptides, X1, X1′, X1″, X2, X3, X4, X5, X6 and Z and the integers m and n are as defined in WO 97/40070, published Oct. 30, 1997, which is also incorporated by reference. Xaa and Yaa below are as defined in WO 98/09985, published Mar. 12, 1998, which is incorporated by reference. AA1, AA2, AB1, AB2, and AC are as defined in International application WO 98/53842, published Dec. 3, 1998, which is incorporated by reference. X1, X2, X3, and X4 in Table 17 only are as defined in
European application EP 0 911 393, published Apr. 28, 1999. Residues appearing in boldface are D-amino acids. All peptides are linked through peptide bonds unless otherwise noted. Abbreviations are listed at the end of this specification. In the “SEQ ID NO.” column, “NR” means that no sequence listing is required for the given sequence.TABLE 4 IL-1 antagonist peptide sequences Sequence/structure SEQ ID NO: Z11Z7Z8QZ5Y4Z9Z10 212 XXQZ5YZ6XX 907 Z7XQZ5YZ6XX 908 Z7Z8QZ5YZ6Z9Z10 909 Z11Z7Z8QZ5YZ6Z9Z10 910 Z12Z13Z14Z15Z16Z17Z18Z19Z20Z21Z22Z11Z7Z8QZ5YZ6Z9Z10L 917 Z23NZ24Z39Z25Z26Z27Z28Z29Z30Z40 979 TANVSSFEWTPYYWQPYALPL 213 SWTDYGYWQPYALPISGL 214 ETPFTWEESNAYYWQPYALPL 215 ENTYSPNWADSMYWQPYALPL 216 SVGEDHNFWTSEYWQPYALPL 217 DGYDRWRQSGERYWQPYALPL 218 FEWTPGYWQPY 219 FEWTPGYWQHY 220 FEWTPGWYQJY 221 AcFEWTPGWYQJY 222 FEWTPGWpYQJY 223 FAWTPGYWQJY 224 FEWAPGYWQJY 225 FEWVPGYWQJY 226 FEWTPGYWQJY 227 AcFEWTPGYWQJY 228 FEWTPaWYQJY 229 FEWTPSarWYQJY 230 FEWTPGYYQPY 231 FEWTPGWWQPY 232 FEWTPNYWQPY 233 FEWTPvYWQJY 234 FEWTPecGYWQJY 235 FEWIPAibYWQJY 236 FEWTSarGYWQJY 237 FEWTPGYWQPY 238 FEWTPGYWQHY 239 FEWTPGWYQJY 240 AcFEWTPGWYQJY 241 FEWTPGW-pY-QJY 242 FAWTPGYWQJY 243 FEWAPGYWQJY 244 FEWVPGYWQJY 245 FEWTPGYWQJY 246 AcFEWTPGYWQJY 247 FEWTPAWYQJY 248 FEWTPSarWYQJY 249 FEWTPGYYQPY 250 FEWTPGWWQPY 251 FEWTPNYWQPY 252 FEWTPVYWQJY 253 FEWTPecGYWQJY 254 FEWTPAibYWQJY 255 FEWTSarGYWQJY 256 FEWTPGYWQPYALPL 257 1NapEWTPGYYQJY 258 YEWTPGYYQJY 259 FEWVPGYYQJY 260 FEWTPSYYQJY 261 FEWTPNYYQJY 262 TKPR 263 RKSSK 264 RKQDK 265 NRKQDK 266 RKQDKR 267 ENRKQDKRF 268 VTKFYF 269 VTKFY 270 VTDFY 271 SHLYWQPYSVQ 671 TLVYWQPYSLQT 672 RGDYWQPYSVQS 673 VHVYWQPYSVQT 674 RLVYWQPYSVQT 675 SRVWFQPYSLQS 676 NMVYWQPYSIQT 677 SVVFWQPYSVQT 678 TFVYWQPYALPL 679 TLVYWQPYSIQR 680 RLVYWQPYSVQR 681 SPVFWQPYSIQI 682 WIEWWQPYSVQS 683 SLIYWQPYSLQM 684 TRLYWQPYSVQR 685 RCDYWQPYSVQT 686 MRVFWQPYSVQN 687 KIVYWQPYSVQT 688 RHLYWQPYSVQR 689 ALVWWQPYSEQI 690 SRVWFQPYSLQS 691 WEQPYALPLE 692 QLVWWQPYSVQR 693 DLRYWQPYSVQV 694 ELVWWQPYSLQL 695 DLVWWQPYSVQW 696 NGNYWQPYSFQV 697 ELVYWQPYSIQR 698 ELMYWQPYSVQE 699 NLLYWQPYSMQD 700 GYEWYQPYSVQR 701 SRVWYQPYSVQR 702 LSEQYQPYSVQR 703 GGGWWQPYSVQR 704 VGRWYQPYSVQR 705 VHVYWQPYSVQR 706 QARWYQPYSVQR 707 VHVYWQPYSVQT 708 RSVYWQPYSVQR 709 TRVWFQPYSVQR 710 GRIWFQPYSVQR 711 GRVWFQPYSVQR 712 ARTWYQPYSVQR 713 ARVWWQPYSVQM 714 RLMFYQPYSVQR 715 ESMWYQPYSVQR 716 HFGWWQPYSVHM 717 ARFWWQPYSVQR 718 RLVYWQ PYAPIY 719 RLVYWQ PYSYQT 720 RLVYWQ PYSLPI 721 RLVYWQ PYSVQA 722 SRVWYQ PYAKGL 723 SRVWYQ PYAQGL 724 SRVWYQ PYAMPL 725 SRVWYQ PYSVQA 726 SRVWYQ PYSLGL 727 SRVWYQ PYAREL 728 SRVWYQ PYSRQP 729 SRVWYQ PYFVQP 730 EYEWYQ PYALPL 731 IPEYWQ PYALPL 732 SRIWWQ PYALPL 733 DPLFWQ PYALPL 734 SRQWVQ PYALPL 735 IRSWWQ PYALPL 736 RGYWQ PYALPL 737 RLLWVQ PYALPL 738 EYRWFQ PYALPL 739 DAYWVQ PYALPL 740 WSGYFQ PYALPL 741 NIEFWQ PYALPL 742 TRDWVQ PYALPL 743 DSSWYQ PYALPL 744 IGNWYQ PYALPL 745 NLRWDQ PYALPL 746 LPEFWQ PYALPL 747 DSYWWQ PYALPL 748 RSQYYQ PYALPL 749 ARFWLQ PYALPL 750 NSYFWQ PYALPL 751 RFMYWQPYSVQR 752 AHLFWQPYSVQR 753 WWQPYALPL 754 YYQPYALPL 755 YFQPYALGL 756 YWYQPYALPL 757 RWWQPYATPL 758 GWYQPYALGF 759 YWYQPYALGL 760 IWYQPYAMPL 761 SNMQPYQRLS 762 TFVYWQPY AVGLPAAETACN 763 TFVYWQPY SVQMTITGKVTM 764 TFVYWQPY SSHXXVPXGFPL 765 TFVYWQPY YGNPQWAIHVRH 766 TFVYWQPY VLLELPEGAVRA 767 TFVYWQPY VDYVWPIPIAQV 768 GWYQPYVDGWR 769 RWEQPYVKDGWS 770 EWYQPYALGWAR 771 GWWQPYARGL 772 LFEQPYAKALGL 773 GWEQPYARGLAG 774 AWVQPYATPLDE 775 MWYQPYSSQPAE 776 GWTQPYSQQGEV 777 DWFQPYSIQSDE 778 PWIQPYARGFG 779 RPLYWQPYSVQV 780 TLIYWQPYSVQI 781 RFDYWQPYSDQT 782 WHQFVQPYALPL 783 EWDS VYWQPYSVQ TLLR 784 WEQN VYWQPYSVQ SFAD 785 SDV VYWQPYSVQ SLEM 786 YYDG VYWQPYSVQ VMPA 787 SDIWYQ PYALPL 788 QRIWWQ PYALPL 789 SRIWWQ PYALPL 790 RSLYWQ PYALPL 791 TIIWEQ PYALPL 792 WETWYQ PYALPL 793 SYDWEQ PYALPL 794 SRIWCQ PYALPL 795 EIMFWQ PYALPL 796 DYVWQQ PYALPL 797 MDLLVQ WYQPYALPL 798 GSKVIL WYQPYALPL 799 RQGANI WYQPYALPL 800 GGGDEP WYQPYALPL 801 SQLERT WYQPYALPL 802 ETWVRE WYQPYALPL 803 KKGSTQ WYQPYALPL 804 LQARMN WYQPYALPL 805 EPRSQK WYQPYALPL 806 VKQKWR WYQPYALPL 807 LRRHDV WYQPYALPL 808 RSTASI WYQPYALPL 809 ESKEDQ WYQPYALPL 810 EGLTMK WYQPYALPL 811 EGSREG WYQPYALPL 812 VIEWWQ PYALPL 813 VWYWEQ PYALPL 814 ASEWWQ PYALPL 815 FYEWWQ PYALPL 816 EGWWVQ PYALPL 817 WGEWLQ PYALPL 818 DYVWEQ PYALPL 819 AHTWWQ PYALPL 820 FIEWFQ PYALPL 821 WLAWEQ PYALPL 822 VMEWWQ PYALPL 823 ERMWQ PYALPL 824 NXXWXX PYALPL 825 WGNWYQ PYALPL 826 TLYWEQ PYALPL 827 VWRWEQ PYALPL 828 LLWTQ PYALPL 829 SRIWXX PYALPL 830 SDIWYQ PYALPL 831 WGYYXX PYALPL 832 TSGWYQ PYALPL 833 VHPYXX PYALPL 834 EHSYFQ PYALPL 835 XXIWYQ PYALPL 836 AQLHSQ PYALPL 837 WANWFQ PYALPL 838 SRLYSQ PYALPL 839 GVTFSQ PYALPL 840 SIVWSQ PYALPL 841 SRDLVQ PYALPL 842 HWGH VYWQPYSVQ DDLG 843 SWHS VYWQPYSVQ SVPE 844 WRDS VYWQPYSVQ PESA 845 TWDA VYWQPYSVQ KWLD 846 TPPW VYWQPYSVQ SLDP 847 YWSS VYWQPYSVQ SVHS 848 YWY QPY ALGL 849 YWY QPY ALPL 850 EWI QPY ATGL 851 NWE QPY AKPL 852 AFY QPY ALPL 853 FLY QPY ALPL 854 VCK QPY LEWC 855 ETPFTWEESNAYYWQPYALPL 856 QGWLTWQDSVDMYWQPYALPL 857 FSEAGYTWPENTYWQPYALPL 858 TESPGGLDWAKIYWQPYALPL 859 DGYDRWRQSGERYWQPYALPL 860 TANVSSFEWTPGYWQPYALPL 861 SVGEDHNFWTSE YWQPYALPL 862 MNDQTSEVSTFP YWQPYALPL 863 SWSEAFEQPRNL YWQPYALPL 864 QYAEPSALNDWG YWQPYALPL 865 NGDWATADWSNY YWQPYALPL 866 THDEHI YWQPYALPL 867 MLEKTYTTWTPG YWQPYALPL 868 WSDPLTRDADL YWQPYALPL 869 SDAFTTQDSQAM YWQPYALPL 870 GDDAAWRTDSLT YWQPYALPL 871 AIIRQLYRWSEM YWQPYALPL 872 ENTYSPNWADSM YWQPYALPL 873 MNDQTSEVSTFP YWQPYALPL 874 SVGEDHNFWTSE YWQPYALPL 875 QTPFTWEESNAY YWQPYALPL 876 ENPFTWQESNAY YWQPYALPL 877 VTPFTWEDSNVF YWQPYALPL 878 QIPFTWEQSNAY YWQPYALPL 879 QAPLTWQESAAY YWQPYALPL 880 EPTFTWEESKAT YWQPYALPL 881 TTTLTWEESNAY YWQPYALPL 882 ESPLTWEESSAL YWQPYALPL 883 ETPLTWEESNAY YWQPYALPL 884 EATFTWAESNAY YWQPYALPL 885 EALFTWKESTAY YWQPYALPL 886 STP-TWEESNAY YWQPYALPL 887 ETPFTWEESNAY YWQPYALPL 888 KAPFTWEESQAY YWQPYALPL 889 STSFTWEESNAY YWQPYALPL 890 DSTFTWEESNAY YWQPYALPL 891 YIPFTWEESNAY YWQPYALPL 892 QTAFTWEESNAY YWQPYALPL 893 ETLFTWEESNAT YWQPYALPL 894 VSSFTWEESNAY YWQPYALPL 895 QPYALPL 896 Py-1-NapPYQJYALPL 897 TANVSSFEWTPG YWQPYALPL 898 FEWTPGYWQPYALPL 899 FEWTPGYWQJYALPL 900 FEWTPGYYQJYALPL 901 ETPFTWEESNAYYWQPYALPL 902 FTWEESNAYYWQJYALPL 903 ADVL YWQPYA PVTLWV 904 GDVAE YWQPYA LPLTSL 905 SWTDYG YWQPYA LPISGL 906 FEWTPGYWQPYALPL 911 FEWTPGYWQJYALPL 912 FEWTPGWYQPYALPL 913 FEWTPGWYQJYALPL 914 FEWTPGYYQPYALPL 915 FEWTPGYYQJYALPL 916 TANVSSFEWTPGYWQPYALPL 918 SWTDYGYWQPYALPISGL 919 ETPFTWEESNAYYWQPYALPL 920 ENTYSPNWADSMYWQPYALPL 921 SVGEDHNFWTSEYWQPYALPL 922 DGYDRWRQSGERYWQPYALPL 923 FEWTPGYWQPYALPL 924 FEWTPGYWQPY 925 FEWTPGYWQJY 926 EWTPGYWQPY 927 FEWTPGWYQJY 928 AEWTPGYWQJY 929 FAWTPGYWQJY 930 FEATPGYWQJY 931 FEWAPGYWQJY 932 FEWTAGYWQJY 933 FEWTPAYWQJY 934 FEWTPGAWQJY 935 FEWTPGYAQJY 936 FEWTPGYWQJA 937 FEWTGGYWQJY 938 FEWTPGYWQJY 939 FEWTJGYWQJY 940 FEWTPecGYWQJY 941 FEWTPAibYWQJY 942 FEWTPSarWYQJY 943 FEWTSarGYWQJY 944 FEWTPNYWQJY 945 FEWTPVYWQJY 946 FEWTVPYWQJY 947 AcFEWTPGWYQJY 948 AcFEWTPGYWQJY 949 INap-EWTPGYYQJY 950 YEWTPGYYQJY 951 FEWVPGYYQJY 952 FEWTPGYYQJY 953 FEWTPsYYQJY 954 FEWTPnYYQJY 955 SHLY-Nap-QPYSVQM 956 TLVY-Nap-QPYSLQT 957 RGDY-Nap-QPYSVQS 958 NMVY-Nap-QPYSIQT 959 VYWQPYSVQ 960 VY-Nap-QPYSVQ 961 TFVYWQJYALPL 962 FEWTPGYYQJ-Bpa 963 XaaFEWTPGYYQJ-Bpa 964 FEWTPGY-Bpa-QJY 965 AcFEWTPGY-Bpa-QJY 966 FEWTPG-Bpa-YQJY 967 AcFEWTPG-Bpa-YQJY 968 AcFE-Bpa-TPGYYQJY 969 AcFE-Bpa-TPGYYQJY 970 Bpa-EWTPGYYQJY 971 AcBpa-EWTPGYYQJY 972 VYWQPYSVQ 973 RLVYWQPYSVQR 974 RLVY-Nap-QPYSVQR 975 RLDYWQPYSVQR 976 RLVWFQPYSVQR 977 RLVYWQPYSIQR 978 DNSSWYDSFLL 980 DNTAWYESFLA 981 DNTAWYENFLL 982 PARE DNTAWYDSFLI WC 983 TSEY DNTTWYEKFLA SQ 984 SQIP DNTAWYQSFLL HG 985 SPFI DNTAWYENFLL TY 986 EQIY DNTAWYDHFLL SY 987 TPFI DNTAWYENFLL TY 988 TYTY DNTAWYERFLM SY 989 TMTQ DNTAWYENFLL SY 990 TI DNTAWYANLVQ TYPQ 991 TI DNTAWYERFLA QYPD 992 HI DNTAWYENFLL TYTP 993 SQ DNTAWYENFLL SYKA 994 QI DNTAWYERFLL QYNA 995 NQ DNTAWYESFLL QYNT 996 TI DNTAWYENFLL NHNL 997 HY DNTAWYERFLQ QGWH 998 ETPFTWEESNAYYWQPYALPL 999 YIPFTWEESNAYYWQPYALPL 1000 DGYDRWRQSGERYWQPYALPL 1001 pY-INap-pY-QJYALPL 1002 TANVSSFEWTPGYWQPYALPL 1003 FEWTPGYWQJYALPL 1004 FEWTPGYWQPYALPLSD 1005 FEWTPGYYQJYALPL 1006 FEWTPGYWQJY 1007 AcFEWTPGYWQJY 1008 AcFEWTPGWYQJY 1009 AcFEWTPGYYQJY 1010 AcFEWTPaYWQJY 1011 AcFEWTPaWYQJY 1012 AcFEWTPaYYQJY 1013 FEWTPGYYQJYALPL 1014 FEWTPGYWQJYALPL 1015 FEWTPGWYQJYALPL 1016 TANVSSFEWTPGYWQPYALPL 1017 AcFEWTPGYWQJY 1018 AcFEWTPGWYQJY 1019 AcFEWTPGYYQJY 1020 AcFEWTPAYWQJY 1021 AcFEWTPAWYQJY 1022 AcFEWTPAYYQJY 1023 -
TABLE 5 EPO-mimetic peptide sequences SEQ Sequence/structure ID NO: YXCXXGPXTWXCXP 83 YXCXXGPXTWXCXP-YXCXXGPXTWXCXP 84 YXCXXGPXTWXCXP-Λ-YXCXXGPXTWXCXP 85 86 86 GGTYSCHFGPLTWVCKPQGG 87 GGDYHCRMGPLTWVCKPLGG 88 GGVYACRMGPITWVCSPLGG 89 VGNYMCHFGPITWVCRPGGG 90 GGLYLCRFGPVTWDCGYKGG 91 GGTYSCHFGPLTWVCKPQGG- 92 GGTYSCHFGPLTWVCKPQGG GGTYSCHFGPLTWVCKPQGG-Λ- 93 GGTYSCHFGPLTWVCKPQGG GGTYSCHFGPLTWVCKPQGGSSK 94 GGTYSCHFGPLTWVCKPQGGSSK- 95 GGTYSCHFGPLTWVCKPQGGSSK GGTYSCHFGPLTWVCKPQGGSSK-Λ- 96 GGTYSCHFGPLTWVCKPQGGSSK 97 97 GGTYSCHFGPLTWVCKPQGGSSK(-Λ-biotin) 98 CX4X5GPX6TWX7C 421 GGTYSCHGPLTWVCKPQGG 422 VGNYMAHMGPITWVGRPGG 423 GGPHHVYACRMGPLTWIC 424 GGTYSCHFGPLTWVCKPQ 425 GGLYACHMGPMTWVCQPLRG 426 TIAQYICYMGPETWECRPSPKA 427 YSCHFGPLTWVCK 428 YCHFGPLTWVC 429 X3X4X5GPX6TWX7X8 124 YX2X3X4X5GPX6TWX7X8 461 X1YX2X3X4X5GPX6TWX7X8X9X10X11 419 X1YX2CX4X5GPX6TWX7CX9X10X11 420 GGLYLCRFGPVTWDCGYKGG 1024 GGTYSCHFGPLTWVCKPQGG 1025 GGDYHCRMGPLTWVCKPLGG 1026 VGNYMCHFGPITWVCRPGGG 1029 GGVYACRMGPITWVCSPLGG 1030 VGNYMAHMGPITWVCRPGG 1035 GGTYSCHFGPLTWVCKPQ 1036 GGLYACHMGPMTWVCQPLRG 1037 TIAQYICYMGPETWECRPSPKA 1038 YSCHFGPLTWVCK 1039 YCHFGPLTWVC 1040 SCHFGPLTWVCK 1041 (AX2)nX3X4X5GPX6TWX7X8 1042 -
TABLE 6 TPO-mimetic peptide sequences SEQ Sequence/structure ID NO: IEGPTLRQWLAARA 13 IEGPTLRQWLAAKA 24 IEGPTLREWLAARA 25 IEGPTLRQWLAARA-Λ-IEGPTLRQWLAARA 26 IEGPTLRQWLAAKA-Λ-IEGPTLRQWLAAKA 27 28 IEGPTLRQWLAARA-Λ-K(BrAc)-Λ-IEGPTLRQWLAARA 29 IEGPTLRQWLAARA-Λ-K(PEG)-Λ- IEGPTLRQWLAARA 30 31 31 32 32 VRDQIXXXL 33 TLREWL 34 GRVRDQVAGW 35 GRVKDQIAQL 36 GVRDQVSWAL 37 ESVREQVMKY 38 SVRSQISASL 39 GVRETVYRHM 40 GVREVIVMHML 41 GRVRDQIWAAL 42 AGVRDQILIWL 43 GRVRDQIMLSL 44 GRVRDQI(X)3 L 45 CTLRQWLQGC 46 CTLQEFLEGC 47 CTRTEWLHGC 48 CTLREWLHGGFC 49 CTLREWVFAGLC 50 CTLRQWLILLGMC 51 CTLAEFLASGVEQC 52 CSLQEFLSHGGYVC 53 CTLREFLDPTTAVC 54 CTLKEWLVSHEVWC 55 CTLREWL(X)2-6C 56-60 REGPTLRQWM 61 EGPTLRQWLA 62 ERGPFWAKAC 63 REGPRCVMWM 64 CGTEGPTLSTWLDC 65 CEQDGPTLLEWLKC 66 CELVGPSLMSWLTC 67 CLTGPFVTQWLYEC 68 CRAGPTLLEWLTLC 69 CADGPTLREWISFC 70 C(X)1-2EGPTLREWL(X)1-2C 71-74 GGCTLREWLHGGFCGG 75 GGCADGPTLREWISFCGG 76 GNADGPTLRQWLEGRRPKN 77 LAIEGPTLRQWLHGNGRDT 78 HGRVGPTLREWKTQVATKK 79 TIKGPTLRQWLKSREHTS so ISDGPTLKEWLSVTRGAS 81 SIEGPTLREWLTSRTPHS 82 -
-
TABLE 8 TNF-antagonist peptide sequences SEQ Sequence/structure ID NO: YCFTASENHCY 106 YCFTNSENHCY 107 YCFTRSENHGY 108 FCASENHCY 109 YCASENHCY 110 FCNSENHCY 111 FCNSENRCY 112 FCNSVENRCY 113 YCSQSVSNDCF 114 FCVSNDRCY 115 YCRKELGQVCY 116 YCKEPGQCY 117 YCRKEMGCY 118 FCRKEMGCY 119 YCWSQNLCY 120 YCELSQYLCY 121 YCWSQNYCY 122 YCWSQYLCY 123 DFLPHYKNTSLGHRP 1085 NR -
TABLE 9 Integrin-binding peptide sequences Sequence/structure SEQ ID NO: RX1ETX2WX3 441 RX1ETX2WX3 442 RGDGX 443 CRGDGXC 444 CX1X2RLDX3X4C 445 CARRLDAPC 446 CPSRLDSPC 447 X1X2X3RGDX4X5X6 448 CX2CRGDCX5C 449 CDCRGDCFC 450 CDGRGDCLC 451 CLCRGDCIC 452 X1X2DDX4X5X7X8 453 X1X2X3DDX4X5X6X7X8 454 CWDDGWLC 455 CWDDLWWLC 456 CWDDGLMC 457 CWDDGWMC 458 CSWDDGWLC 459 CPDDLWWLC 460 NGR NR GSL NR RGD NR CGRECPRLCQSSC 1071 CNGRCVSGCAGRC 1072 CLSGSLSC 1073 RGD NR NGR NR GSL NR NGRAHA 1074 CNGRC 1075 CDCRGDCFC 1076 CGSLVRC 1077 DLXXL 1043 RTDLDSLRTYTL 1044 RTDLDSLRTY 1053 RTDLDSLRT 1054 RTDLDSLR 1078 GDLDLLKLRLTL 1079 GDLHSLRQLLSR 1080 RDDLHMLRLQLW 1081 SSDLHALKKRYG 1082 RGDLKQLSELTW 1083 RGDLAALSAPPV 1084 -
TABLE 10 Selectin antagonist peptide sequences Sequence/structure SEQ ID NO: DITWDQLWDLMK 147 DITWDELWKIMN 148 DYTWFELWDMMQ 149 QITWAQLWNMMK 150 DMTWHDLWTLMS 151 DYSWHDLWEMMS 152 EITWDQLWEVMN 153 HVSWEQLWDIMN 154 HITWDQLWRIMT 155 RNMSWLELWEHMK 156 AEWTWDQLWHVMNPAESQ 157 HRAEWLALWEQMSP 158 KKEDWLALWRIMSV 159 ITWDQLWDLMK 160 DITWDQLWDLMK 161 DITWDQLWDLMK 162 DITWDQLWDLMK 163 CQNRYTDLVAIQNKNE 462 AENWADNEPNNKRNNED 463 RKNNKTWTWVGTKKALTNE 464 KKALTNEAENWAD 465 CQXRYTDLVAIQNKXE 466 RKXNXXWTWVGTXKXLTEE 467 AENWADGEPNNKXNXED 468 CXXXYTXLVAIQNKXE 469 RKXXXXWXWVGTXKXLTXE 470 AXNWXXXEPNNXXXED 471 XKXKTXEAXNWXX 472 -
TABLE 11 Antipathogenic peptide sequences Sequence/structure SEQ ID NO: GFFALIPKIISSPLFKTLLSAVGSALSSSGGQQ 503 GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE 504 GFFALIPKIISSPLFKTLLSAV 505 GFFALIPKIISSPLFKTLLSAV 506 KGFFALIPKIISSPLFKTLLSAV 507 KKGFFALIPKIISSPLFKTLLSAV 508 KKGFFALIPKIISSPLFKTLLSAV 509 GFFALIPKIIS 510 GIGAVLKVLTTGLPALISWIKRKRQQ 511 GIGAVLKVLTTGLPALISWIKRKRQQ 512 GIGAVLKVLTTGLPALISWIKRKRQQ 513 GIGAVLKVLTTGLPALISWIKR 514 AVLKVLTTGLPALISWIKR 515 KLLLLLKLLLLK 516 KLLLKLLLKLLK 517 KLLLKLKLKLLK 518 KKLLKLKLKLKK 519 KLLLKLLLKLLK 520 KLLLKLKLKLLK 521 KLLLLK 522 KLLLKLLK 523 KLLLKLKLKLLK 524 KLLLKLKLKLLK 525 KLLLKLKLKLLK 526 KAAAKAAAKAAK 527 KVVVKVVVKVVK 528 KVVVKVKVKVVK 529 KVVVKVKVKVK 530 KVVVKVKVKVVK 531 KLILKL 532 KVLHLL 533 LKLRLL 534 KPLHLL 535 KLILKLVR 536 KVFHLLHL 537 HKFRILKL 538 KPFHILHL 539 KIIIKIKIKIIK 540 KIIIKIKIKIIK 541 KIIIKIKIKIIK 542 KIPIKIKIKIPK 543 KIPIKIKIKIVK 544 RIIIRIRIRIIR 545 RIIIRIRIRIIR 546 RIIIRIRIRIIR 547 RIVIRIRIRLIR 548 RIIVRIRLRIIR 549 RIGIRLRVRIIR 550 KIVIRIRIRLIR 551 RIAVKWRLRFIK 552 KIGWKLRVRIIR 553 KKIGWLIIRVRR 554 RIVIRIRIRLIRIR 555 RIIVRIRLRIIRVR 556 RIGIRLRVRIIRRV 557 KIVIRIRARLIRIRIR 558 RIIVKIRLRIIKKIRL 559 KIGIKARVRIIRVKII 560 RIIVHIRLRIIHHIRL 561 HIGIKAHVRIIRVHII 562 RIYVKIHLRYIKKIRL 563 KIGHKARVHIIRYKII 564 RIYVKPHPRYIKKIRL 565 KPGHKARPHIIRYKII 566 KIVIRIRIRLIRIRIRKIV 567 RIIVKIRLRIIKKIRLIKK 568 KIGWKLRVRIIRVKIGRLR 569 KIVIRIRIRLIRIRIRKIVKVKRIR 570 RFAVKIRLRIIKKIRLIKKIRKRVIK 571 KAGWKLRVRIIRVKIGRLRKIGWKKRVRIK 572 RIYVKPHPRYIKKIRL 573 KPGHKARPHIIRYKII 574 KIVIRIRIRLIRIRIRKIV 575 RIIVKIRLRIIKKIRLIKK 576 RIYVSKISIYIKKIRL 577 KIVIFTRIRLTSIRIRSIV 578 KPIHKARPTIIRYKMI 579 cyclicCKGFFALIPKIISSPLFKTLLSAVC 580 CKKGFFALIPKIISSPLFKTLLSAVC 581 CKKKGFFALIPKIISSPLFKTLLSAVC 582 CyclicCRIVIRIRIRLIRIRC 583 CyclicCKPGHKARPHIIRYKIIC 584 CyclicCRFAVKIRLRIIKKIRLIKKIRKAVIKC 585 KLLLKLLL KLLKC 586 KLLLKLLLKLLK 587 KLLLKLKLKLLKC 588 KLLLKLLLKLLK 589 -
TABLE 12 VIP-mimetic peptide sequences SEQ Sequence/structure ID NO: HSDAVFYDNYTR LRKQMAVKKYLN SILN 590 Nle HSDAVFYDNYTR LRKQMAVKKYLN SILN 591 X1X1′X1″X2 592 X3 S X4 LN 593 594 KKYL 595 NSILN 596 KKYL 597 KKYA 598 AVKKYL 599 NSILN 600 KKYV 601 SILauN 602 KKYLNle 603 NSYLN 604 NSIYN 605 KKYLPPNSILN 606 LauKKYL 607 CapKKYL 608 KYL NR KKYNle 609 VKKYL 610 LNSILN 611 YLNSILN 612 KKYLN 613 KKYLNS 614 KKYLNSI 615 KKYLNSIL 616 KKYL 617 KKYDA 618 AVKKYL 619 NSILN 620 KKYV 621 SILauN 622 NSYLN 623 NSIYN 624 KKYLNle 625 KKYLPPNSILN 626 KKYL 627 KKYDA 628 AVKKYL 629 NSILN 630 KKYV 631 SILauN 632 LauKKYL 633 CapKKYL 634 KYL NR KYL NR KKYNle 635 VKKYL 636 LNSILN 637 YLNSILN 638 KKYLNle 639 KKYLN 640 KKYLNS 641 KKYLNSI 642 KKYLNSIL 643 KKKYLD 644 cyclicCKKYLC 645 646 KKYA 647 WWTDTGLW 648 WWTDDGLW 649 WWDTRGLWVWTI 650 FWGNDGIWLESG 651 DWDQFGLWRGAA 652 RWDDNGLWVVVL 653 SGMWSHYGIWMG 654 GGRWDQAGLWVA 655 KLWSEQGIWMGE 656 CWSMHGLWLC 657 GCWDNTGIWVPC 658 DWDTRGLWVY 659 SLWDENGAWI 660 KWDDRGLWMH 661 QAWNERGLWT 662 QWDTRGLWVA 663 WNVHGIWQE 664 SWDTRGLWVE 665 DWDTRGLWVA 666 SWGRDGLWIE 667 EWTDNGLWAL 668 SWDEKGLWSA 669 SWDSSGLWMD 670 -
TABLE 13 Mdm/hdm antagonist peptide sequences Sequence/structure SEQ ID NO: TFSDLW 130 QETFSDLWKLLP 131 QPTFSDLWKLLP 132 QETFSDYWKLLP 133 QPTFSDYWKLLP 134 MPRFMDYWEGLN 135 VQNFIDYWTQQF 136 TGPAFTHYWATF 137 IDRAPTFRDHWFALV 138 PRPALVFADYWETLY 139 PAFSRFWSDLSAGAH 140 PAFSRFWSKLSAGAH 141 PXFXDYWXXL 142 QETFSDLWKLLP 143 QPTFSDLWKLLP 144 QETFSDYWKLLP 145 QPTFSDYWKLLP 146 -
TABLE 14 Calmodulin antagonist peptide sequences Sequence/structure SEQ ID NO: SCVKWGKKEFCGS 164 SCWKYWGKECGS 165 SCYEWGKLRWCGS 166 SCLRWGKWSNCGS 167 SCWRWGKYQICGS 168 SCVSWGALKLCGS 169 SCIRWGQNTFCGS 170 SCWQWGNLKICGS 171 SCVRWGQLSICGS 172 LKKFNARRKLKGAILTTMLAK 173 RRWKKNFIAVSAANRFKK 174 RKWQKTGHAVRAIGRLSS 175 INLKALAALAKKIL 176 KIWSILAPLGTTLVKLVA 177 LKKLLKLLKKLLKL 178 LKWKKLLKLLKKLLKKLL 179 AEWPSLTEIKTLSHFSV 180 AEWPSPTRVISTTYFGS 181 AELAHWPPVKTVLRSFT 182 AEGSWLQLLNLMKQMNN 183 AEWPSLTEIK 184 -
TABLE 15 Mast cell antagonists/Mast cell protease inhibitor peptide sequences Sequence/structure SEQ ID NO: SGSGVLKRPLPILPVTR 272 RWLSSRPLPPLPLPPRT 273 GSGSYDTLALPSLPLHPMSS 274 GSGSYDTRALPSLPLHPMSS 275 GSGSSGVTMYPKLPPHWSMA 276 GSGSSGVRMYPKLPPHWSMA 277 GSGSSSMRMVPTIPGSAKHG 278 RNR NR QT NR RQK NR NRQ NR RQK NR RNRQKT 436 RNRQ 437 RNRQK 438 NRQKT 439 RQKT 440 -
TABLE 16 SH3 antagonist peptide sequences Sequence/structure SEQ ID NO: RPLPPLP 282 RELPPLP 283 SPLPPLP 284 GPLPPLP 285 RPLPIPP 286 RPLPIPP 287 RRLPPTP 288 RQLPPTP 289 RPLPSRP 290 RPLPTRP 291 SRLPPLP 292 RALPSPP 293 RRLPRTP 294 RPVPPIT 295 ILAPPVP 296 RPLPMLP 297 RPLPILP 298 RPLPSLP 299 RPLPSLP 300 RPLPMIP 301 RPLPLIP 302 RPLPPTP 303 RSLPPLP 304 RPQPPPP 305 RQLPIPP 306 XXXRPLPPLPXP 307 XXXRPLPPIPXX 308 XXXRPLPPLPXX 309 RXXRPLPPLPXP 310 RXXRPLPPLPPP 311 PPPYPPPPIPXX 312 PPPYPPPPVPXX 313 LXXRPLPXΨP 314 ΨPXXRPLPXLP 315 PPXΘPPPΨP 316 +PPΨPXKPXWL 317 RPXΨPΨR+SXP 318 PPVPPRPXXTL 319 ΨPΨLPΨK 320 +ΘDXPLPXLP 321 -
TABLE 17 Somatostatin or cortistatin mimetic peptide sequences Sequence/structure SEQ ID NO: X1-X2-Asn-Phe-Phe-Trp-Lys-Thr-Phe-X3-Ser-X4 473 Asp Arg Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 474 Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 475 Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 476 Asp Arg Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 477 Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 478 Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 479 Asp Arg Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 480 Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 481 Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 482 Asp Arg Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 483 Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 484 Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 485 Asp Arg Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 486 Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 487 Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 488 Asp Arg Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 489 Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 490 Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 491 Asp Arg Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 492 Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 493 Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 494 Asp Arg Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 495 Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 496 Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 497 -
TABLE 18 UKR antagonist peptide sequences Sequence/structure SEQ ID NO: AEPMPHSLNFSQYLWYT 196 AEHTYSSLWDTYSPLAF 197 AELDLWMRHYPLSFSNR 198 AESSLWTRYAWPSMPSY 199 AEWHPGLSFGSYLWSKT 200 AEPALLNWSFFFNPGLH 201 AEWSFYNLHLPEPQTIF 202 AEPLDLWSLYSLPPLAM 203 AEPTLWQLYQFPLRLSG 204 AEISFSELMWLRSTPAF 205 AELSEADLWTTWFGMGS 206 AESSLWRIFSPSALMMS 207 AESLPTLTSILWGKESV 208 AETLFMDLWHDKHILLT 209 AEILNFPLWHEPLWSTE 210 AESQTGTLNTLFWNTLR 211 AEPVYQYELDSYLRSYY 430 AELDLSTFYDIQYLLRT 431 AEFFKLGPNGYVYLHSA 432 FKLXXXGYVYL 433 AESTYHHLSLGYMYTLN 434 YHXLXXGYMYT 435 -
TABLE 19 Macrophage and/or T-cell inhibiting peptide sequences Sequence/structure SEQ ID NO: Xaa-Yaa-Arg NR Arg-Yaa-Xaa NR Xaa-Arg-Yaa NR Yaa-Arg-Xaa NR Ala-Arg NR Arg-Arg NR Asn-Arg NR Asp-Arg NR Cys-Arg NR Gln-Arg NR Glu-Arg NR Gly-Arg NR His-arg NR Ile-Arg NR Leu-Arg NR Lys-Arg NR Met-Arg NR Phe-Arg NR Ser-Arg NR Thr-Arg NR Trp-Arg NR Tyr-Arg NR Val-Arg NR Ala-Glu-Arg NR Arg-Glu-Arg NR Asn-Glu-Arg NR Asp-Glu-Arg NR Cys-Glu-Arg NR Gln-Glu-Arg NR Glu-Glu-Arg NR Gly-Glu-Arg NR His-Glu-Arg NR IIe-Glu-Arg NR Leu-Glu-Arg NR Lys-Glu-Arg NR Met-Glu-Arg NR Phe-Glu-Arg NR Pro-Glu-Arg NR Ser-Glu-Arg NR Thr-Glu-Arg NR Trp-Glu-Arg NR Tyr-Glu-Arg NR Val-Glu-Arg NR Arg-Ala NR Arg-Asp NR Arg-Cys NR Arg-Gln NR Arg-Glu NR Arg-Gly NR Arg-His NR Arg-Ile NR Arg-Leu NR Arg-Lys NR Arg-Met NR Arg-Phe NR Arg-Pro NR Arg-Ser NR Arg-Thr NR Arg-Trp NR Arg-Tyr NR Arg-Val NR Arg-Glu-Ala NR Arg-Glu-Asn NR Arg-Glu-Asp NR Arg-Glu-Cys NR Arg-Glu-Gln NR Arg-Glu-Glu NR Arg-Glu-Gly NR Arg-Glu-His NR Arg-Glu-Ile NR Arg-Glu-Leu NR Arg-Glu-Lys NR Arg-Glu-Met NR Arg-Glu-Phe NR Arg-Glu-Pro NR Arg-Glu-Ser NR Arg-Glu-Thr NR Arg-Glu-Trp NR Arg-Glu-Tyr NR Arg-Glu-Val NR Ala-Arg-Glu NR Arg-Arg-Glu NR Asn-Arg-Glu NR Asp-Arg-Glu NR Cys-Arg-Glu NR Gln-Arg-Glu NR Glu-Arg-Glu NR Gly-Arg-Glu NR His-Arg-Glu NR Ile-Arg-Glu NR Leu-Arg-Glu NR Lys-Arg-Glu NR Met-Arg-Glu NR Phe-Arg-Glu NR Pro-Arg-Glu NR Ser-Arg-Glu NR Thr-Arg-Glu NR Trp-Arg-Glu NR Tyr-Arg-Glu NR Val-Arg-Glu NR Glu-Arg-Ala NR Glu-Arg-Arg NR Glu-Arg-Asn NR Glu-Arg-Asp NR Glu-Arg-Cys NR Glu-Arg-Gln NR Glu-Arg-Gly NR Glu-Arg-His NR Glu-Arg-Ile NR Glu-Arg-Leu NR Glu-Arg-Lys NR Glu-Arg-Met NR Glu-Arg-Phe NR Glu-Arg-Pro NR Glu-Arg-Ser NR Glu-Arg-Thr NR Glu-Arg-Trp NR Glu-Arg-Tyr NR Glu-Arg-Val NR -
TABLE 20 Additional Exemplary Pharmacologically Active Peptides SEQ ID Sequence/structure NO: Activity VEPNCDIHVMWEWECFERL 1027 VEGF-antagonist GERWCFDGPLTWVCGEES 1084 VEGF-antagonist RGWVEICVADDNGMCVTEAQ 1085 VEGF-antagonist GWDECDVARMWEWECFAGV 1086 VEGF-antagonist GERWCFDGPRAWVCGWEI 501 VEGF-antagonist EELWCFDGPRAWVCGYVK 502 VEGF-antagonist RGWVEICAADDYGRCLTEAQ 1031 VEGF-antagonist RGWVEICESDVWGRCL 1087 VEGF-antagonist RGWVEICESDVWGRCL 1088 VEGF-antagonist GGNECDIARMWEWECFERL 1089 VEGF-antagonist RGWVEICAADDYGRCL 1090 VEGF-antagonist CTTHWGFTLC 1028 MMP inhibitor CLRSGXGC 1091 MMP inhibitor CXXHWGFXXC 1092 MMP inhibitor CXPXC 1093 MMP inhibitor CRRHWGFEFC 1094 MMP inhibitor STTHWGFTLS 1095 MMP inhibitor CSLHWGFWWC 1096 CTLA4-mimetic GFVCSGIFAVGVGRC 125 CTLA4-mimetic APGVRLGCAVLGRYC 126 CTLA4-mimetic LLGRMK 105 Antiviral (HBV) ICVVQDWGHHRCTAGHMANLTSHASAI 127 C3b antagonist ICVVQDWGHHRCT 128 C3b antagonist CVVQDWGHHAC 129 C3b antagonist STGGFDDVYDWARGVSSALTTTLVATR 185 Vinculin-binding STGGFDDVYDWARRVSSALTTTLVATR 186 Vinculin-binding SRGVNFSEWLYDMSAAMKEASNVFPSRRSR 187 Vinculin-binding SSQNWDMEAGVEDLTAAMLGLLSTIHSSSR 188 Vinculin-binding SSPSLYTQFLVNYESAATRIQDLLIASRPSR 189 Vinculin-binding SSTGWVDLLGALQRAADATRTSIPPSLQNSR 190 Vinculin-binding DVYTKKELIECARRVSEK 191 Vinculin-binding EKGSYYPGSGIAQFHIDYNNVS 192 C4BP-binding SGIAQFHIDYNNVSSAEGWHVN 193 C4BP-binding LVTVEKGSYYPGSGIAQFHIDYNNVSSAEGWHVN 194 C4BP-binding SGIAQFHIDYNNVS 195 C4BP-binding LLGRMK 279 anti-HBV ALLGRMKG 280 anti-HBV LDPAFR 281 anti-HBV CXXRGDC 322 Inhibition of platelet aggregation RPLPPLP 323 Src antagonist PPVPPR 324 Src antagonist XFXDXWXXLXX 325 Anti-cancer (particularly for sarcomas) KACRRLFGPVDSEQLSRDCD 326 p16-mimetic RERWNFDFVTETPLEGDFAW 327 p16-mimetic KRRQTSMTDFYHSKRRLIFS 328 p16-mimetic TSMTDFYHSKRRLIFSKRKP 329 p16-mimetic RRLIF 330 p16-mimetic KRRQTSATDFYHSKRRLIFSRQIKIWFQNRRMKWKK 331 p16-mimetic KRRLIFSKRQIKIWFQNRRMKWKK 332 p16-mimetic Asn Gln Gly Arg His Phe Cys Gly Gly Ala Leu Ile His Ala 498 CAP37 mimetic/LPS Arg Phe Val Met Thr Ala Ala Ser Cys Phe Gln binding Arg His Phe Cys Gly Gly Ala Leu Ile His Ala Arg Phe Val 499 CAP37 mimetic/LPS Met Thr Ala Ala Ser Cys binding Gly Thr Arg Cys Gln Val Ala Gly Trp Gly Ser Gln Arg Ser 500 CAP37 mimetic/LPS Gly Gly Arg Leu Ser Arg Phe Pro Arg Phe Val Asn Val binding WHWRHRIPLQLAAGR 1097 carbohydrate (GD1 alpha) mimetic LKTPRV 1098 β2GPI Ab binding NTLKTPRV 1099 β2GPI Ab binding NTLKTPRVGGC 1100 β2GPI Ab binding KDKATF 1101 β2GPI Ab binding KDKATFGCHD 1102 β2GPI Ab binding KDKATFGCHDGC 1103 β2GPI Ab binding TLRVYK 1104 β2GPI Ab binding ATLRVYKGG 1105 β2GPI Ab binding CATLRVYKGG 1106 β2GPI Ab binding INLKALAALAKKIL 1107 Membrane- transporting GWT NR Membrane- transporting GWTLNSAGYLLG 1108 Membrane- transporting GWTLNSAGYLLGKINLKALAALAKKIL 1109 Membrane- transporting - The present invention is also particularly useful with peptides having activity in treatment of:
- cancer, wherein the peptide is a VEGF-mimetic or a VEGF receptor antagonist, a HER2 agonist or antagonist, a CD20 antagonist and the like;
- asthma, wherein the protein of interest is a CKR3 antagonist, an IL-5 receptor antagonist, and the like;
- thrombosis, wherein the protein of interest is a GPIIb antagonist, a GPIIIa antagonist, and the like;
- autoimmune diseases and other conditions involving immune modulation, wherein the protein of interest is an IL-2 receptor antagonist, a CD40 agonist or antagonist, a CD40L agonist or antagonist, a thymopoietin mimetic and the like.
- Vehicles. This invention requires the presence of at least one vehicle (F1, F2) attached to a peptide through the N-terminus, C-terminus or a sidechain of one of the amino acid residues. Multiple vehicles may also be used; e.g., Fc's at each terminus or an Fc at a terminus and a PEG group at the other terminus or a sidechain.
- An Fc domain is the preferred vehicle. The Fc domain may be fused to the N or C termini of the peptides or at both the N and C termini. For the TPO-mimetic peptides, molecules having the Fc domain fused to the N terminus of the peptide portion of the molecule are more bioactive than other such fusions, so fusion to the N terminus is preferred. As noted above, Fc variants are suitable vehicles within the scope of this invention. A native Fc may be extensively modified to form an Fc variant in accordance with this invention, provided binding to the salvage receptor is maintained; see, for example WO 97/34631 and WO 96/32478.
- In such Fc variants, one may remove one or more sites of a native Fc that provide structural features or functional activity not required by the fusion molecules of this invention. One may remove these sites by, for example, substituting or deleting residues, inserting residues into the site, or truncating portions containing the site. The inserted or substituted residues may also be altered amino acids, such as peptidomimetics or D-amino acids. Fc variants may be desirable for a number of reasons, several of which are described below. Exemplary Fc variants include molecules and sequences in which:
- 1. Sites involved in disulfide bond formation are removed. Such removal may avoid reaction with other cysteine-containing proteins present in the host cell used to produce the molecules of the invention. For this purpose, the cysteine-containing segment at the N-terminus may be truncated or cysteine residues may be deleted or substituted with other amino acids (e.g., alanyl, seryl). In particular, one may truncate the N-terminal 20-amino acid segment of SEQ ID NO: 2 or delete or substitute the cysteine residues at
positions - 2. A native Fc is modified to make it more compatible with a selected host cell. For example, one may remove the PA sequence near the N-terminus of a typical native Fc, which may be recognized by a digestive enzyme inE. coli such as proline iminopeptidase. One may also add an N-terminal methionine residue, especially when the molecule is expressed recombinantly in a bacterial cell such as E. coli. The Fc domain of SEQ ID NO: 2 (FIG. 4) is one such Fc variant.
- 3. A portion of the N-terminus of a native Fc is removed to prevent N-terminal heterogeneity when expressed in a selected host cell. For this purpose, one may delete any of the first 20 amino acid residues at the N-terminus, particularly those at
positions - 4. One or more glycosylation sites are removed. Residues that are typically glycosylated (e.g., asparagine) may confer cytolytic response. Such residues may be deleted or substituted with unglycosylated residues (e.g., alanine).
- 5. Sites involved in interaction with complement, such as the C1q binding site, are removed. For example, one may delete or substitute the EKK sequence of human IgG1. Complement recruitment may not be advantageous for the molecules of this invention and so may be avoided with such an Fc variant.
- 6. Sites are removed that affect binding to Fc receptors other than a salvage receptor. A native Fc may have sites for interaction with certain white blood cells that are not required for the fusion molecules of the present invention and so may be removed.
- 7. The ADCC site is removed. ADCC sites are known in the art; see, for example,Molec. Immunol. 29 (5): 633-9 (1992) with regard to ADCC sites in IgG1. These sites, as well, are not required for the fusion molecules of the present invention and so may be removed.
- 8. When the native Fc is derived from a non-human antibody, the native Fc may be humanized. Typically, to humanize a native Fc, one will substitute selected residues in the non-human native Fc with residues that are normally found in human native Fc. Techniques for antibody humanization are well known in the art.
- Preferred Fc variants include the following. In SEQ ID NO: 2 (FIG. 4) the leucine at
position 15 may be substituted with glutamate; the glutamate at position 99, with alanine; and the lysines at positions 101 and 103, with alanines. In addition, one or more tyrosine residues can be replaced by phenyalanine residues. - An alternative vehicle would be a protein, polypeptide, peptide, antibody, antibody fragment, or small molecule (e.g., a peptidomimetic compound) capable of binding to a salvage receptor. For example, one could use as a vehicle a polypeptide as described in U.S. Pat. No. 5,739,277, issued Apr. 14, 1998 to Presta et al. Peptides could also be selected by phage display for binding to the FcRn salvage receptor. Such salvage receptor-binding compounds are also included within the meaning of “vehicle” and are within the scope of this invention. Such vehicles should be selected for increased half-life (e.g., by avoiding sequences recognized by proteases) and decreased immunogenicity (e.g., by favoring non-immunogenic sequences, as discovered in antibody humanization).
- As noted above, polymer vehicles may also be used for F1 and F2. Various means for attaching chemical moieties useful as vehicles are currently available, see, e.g., Patent Cooperation Treaty (“PCT”) International Publication No. WO 96/11953, entitled “N-Terminally Chemically Modified Protein Compositions and Methods,” herein incorporated by reference in its entirety. This PCT publication discloses, among other things, the selective attachment of water soluble polymers to the N-terminus of proteins.
- A preferred polymer vehicle is polyethylene glycol (PEG). The PEG group may be of any convenient molecular weight and may be linear or branched. The average molecular weight of the PEG will preferably range from about 2 kiloDalton (“kD”) to about 100 kDa, more preferably from about 5 kDa to about 50 kDa, most preferably from about 5 kDa to about 10 kDa. The PEG groups will generally be attached to the compounds of the invention via acylation or reductive alkylation through a reactive group on the PEG moiety (e.g., an aldehyde, amino, thiol, or ester group) to a reactive group on the inventive compound (e.g., an aldehyde, amino, or ester group).
- A useful strategy for the PEGylation of synthetic peptides consists of combining, through forming a conjugate linkage in solution, a peptide and a PEG moiety, each bearing a special functionality that is mutually reactive toward the other. The peptides can be easily prepared with conventional solid phase synthesis (see, for example, FIGS. 5 and 6 and the accompanying text herein). The peptides are “preactivated” with an appropriate functional group at a specific site. The precursors are purified and fully characterized prior to reacting with the PEG moiety. Ligation of the peptide with PEG usually takes place in aqueous phase and can be easily monitored by reverse phase analytical HPLC. The PEGylated peptides can be easily purified by preparative HPLC and characterized by analytical HPLC, amino acid analysis and laser desorption mass spectrometry.
- Polysaccharide polymers are another type of water soluble polymer which may be used for protein modification. Dextrans are polysaccharide polymers comprised of individual subunits of glucose predominantly linked by α1-6 linkages. The dextran itself is available in many molecular weight ranges, and is readily available in molecular weights from about 1 kD to about 70 kD. Dextran is a suitable water soluble polymer for use in the present invention as a vehicle by itself or in combination with another vehicle (e.g., Fc). See, for example, WO 96/11953 and WO 96/05309. The use of dextran conjugated to therapeutic or diagnostic immunoglobulins has been reported; see, for example, European Patent Publication No. 0 315 456, which is hereby incorporated by reference. Dextran of about 1 kD to about 20 kD is preferred when dextran is used as a vehicle in accordance with the present invention.
- Linkers. Any “linker” group is optional. When present, its chemical structure is not critical, since it serves primarily as a spacer. The linker is preferably made up of amino acids linked together by peptide bonds. Thus, in preferred embodiments, the linker is made up of from 1 to 20 amino acids linked by peptide bonds, wherein the amino acids are selected from the 20 naturally occurring amino acids. Some of these amino acids may be glycosylated, as is well understood by those in the art. In a more preferred embodiment, the 1 to 20 amino acids are selected from glycine, alanine, proline, asparagine, glutamine, and lysine. Even more preferably, a linker is made up of a majority of amino acids that are sterically unhindered, such as glycine and alanine. Thus, preferred linkers are polyglycines (particularly (Gly)4, (Gly)5), poly(Gly-Ala), and polyalanines. Other specific examples of linkers are:
(Gly)3Lys(Gly)4; (SEQ ID NO: 333) (Gly)3AsnGlySer(Gly)2; (SEQ ID NO: 334) (Gly)3Cys(Gly)4; and (SEQ ID NO: 335) GlyProAsnGlyGly. (SEQ ID NO: 336) - To explain the above nomenclature, for example, (Gly)3Lys(Gly)4 means Gly-Gly-Gly-Lys-Gly-Gly-Gly-Gly. Combinations of Gly and Ala are also preferred. The linkers shown here are exemplary; linkers within the scope of this invention may be much longer and may include other residues.
-
- wherein n is such that the linker has a molecular weight of 100 to 5000 kD, preferably 100 to 500 kD. The peptide linkers may be altered to form derivatives in the same manner as described above.
- Derivatives. The inventors also contemplate derivatizing the peptide and/or vehicle portion of the compounds. Such derivatives may improve the solubility, absorption, biological half life, and the like of the compounds. The moieties may alternatively eliminate or attenuate any undesirable side-effect of the compounds and the like. Exemplary derivatives include compounds in which:
- 1. The compound or some portion thereof is cyclic. For example, the peptide portion may be modified to contain two or more Cys residues (e.g., in the linker), which could cyclize by disulfide bond formation. For citations to references on preparation of cyclized derivatives, see Table 2.
- 2. The compound is cross-linked or is rendered capable of cross-linking between molecules. For example, the peptide portion may be modified to contain one Cys residue and thereby be able to form an intermolecular disulfide bond with a like molecule. The compound may also be cross-linked through its C-terminus, as in the molecule shown below.
- 3.
- 4. One or more peptidyl [—C(O)NR—] linkages (bonds) is replaced by a non-peptidyl linkage. Exemplary non-peptidyl linkages are —CH2-carbamate [—CH2—OC(O)NR—], phosphonate, —CH2-sulfonamide [—CH2—S(O)2NR—], urea [—NHC(O)NH—], —CH2-secondary amine, and alkylated peptide [—C(O)NR6— wherein R6 is lower alkyl].
- 5. The N-terminus is derivatized. Typically, the N-terminus may be acylated or modified to a substituted amine. Exemplary N-terminal derivative groups include —NRR1 (other than —NH2), —NRC(O)R1, —NRC(O)OR1, —NRS(O)2R1, —NHC(O)NHR1, succinimide, or benzyloxycarbonyl-NH— (CBZ-NH—), wherein R and R′ are each independently hydrogen or lower alkyl and wherein the phenyl ring may be substituted with 1 to 3 substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, chloro, and bromo.
- 6. The free C-terminus is derivatized. Typically, the C-terminus is esterified or amidated. For example, one may use methods described in the art to add (NH—CH2—CH2—NH2)2 to compounds of this invention having any of SEQ ID NOS: 504 to 508 at the C-terminus. Likewise, one may use methods described in the art to add —NH2 to compounds of this invention having any of SEQ ID NOS: 924 to 955, 963 to 972, 1005 to 1013, or 1018 to 1023 at the C-terminus. Exemplary C-terminal derivative groups include, for example, —C(O)R2 wherein R2 is lower alkoxy or —NR3R4 wherein R3 and R4 are independently hydrogen or C1-C8 alkyl (preferably C1-C4 alkyl).
- 7. A disulfide bond is replaced with another, preferably more stable, cross-linking moiety (e.g., an alkylene). See, e.g., Bhatnagar et al. (1996),J. Med. Chem. 39: 3814-9; Alberts et al. (1993) Thirteenth Am. Pep. Symp., 357-9.
- 8. One or more individual amino acid residues is modified. Various derivatizing agents are known to react specifically with selected sidechains or terminal residues, as described in detail below.
- Lysinyl residues and amino terminal residues may be reacted with succinic or other carboxylic acid anhydrides, which reverse the charge of the lysinyl residues. Other suitable reagents for derivatizing alpha-amino-containing residues include imidoesters such as methyl picolinimidate; pyridoxal phosphate; pyridoxal; chloroborohydride; trinitrobenzenesulfonic acid; O-methylisourea; 2,4 pentanedione; and transaminase-catalyzed reaction with glyoxylate.
- Arginyl residues may be modified by reaction with any one or combination of several conventional reagents, including phenylglyoxal, 2,3-butanedione, 1,2-cyclohexanedione, and ninhydrin. Derivatization of arginyl residues requires that the reaction be performed in alkaline conditions because of the high pKa of the guanidine functional group. Furthermore, these reagents may react with the groups of lysine as well as the arginine epsilon-amino group.
- Specific modification of tyrosyl residues has been studied extensively, with particular interest in introducing spectral labels into tyrosyl residues by reaction with aromatic diazonium compounds or tetranitromethane. Most commonly, N-acetylimidizole and tetranitromethane are used to form O-acetyl tyrosyl species and 3-nitro derivatives, respectively.
- Carboxyl sidechain groups (aspartyl or glutamyl) may be selectively modified by reaction with carbodiimides (R1-N═C═N—R′) such as 1-cyclohexyl-3-(2-morpholinyl-(4-ethyl) carbodiimide or 1-ethyl-3-(4-azonia-4,4-dimethylpentyl) carbodiimide. Furthermore, aspartyl and glutamyl residues may be converted to asparaginyl and glutaminyl residues by reaction with ammonium ions.
- Glutaminyl and asparaginyl residues may be deamidated to the corresponding glutamyl and aspartyl residues. Alternatively, these residues are deamidated under mildly acidic conditions. Either form of these residues falls within the scope of this invention.
- Cysteinyl residues can be replaced by amino acid residues or other moieties either to eliminate disulfide bonding or, conversely, to stabilize cross-linking. See, e.g., Bhatnagar et al. (1996),J. Med. Chem. 39: 3814-9.
- Derivatization with bifunctional agents is useful for cross-linking the peptides or their functional derivatives to a water-insoluble support matrix or to other macromolecular vehicles. Commonly used cross-linking agents include, e.g., 1,1-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3′-dithiobis(succinimidylpropionate), and bifunctional maleimides such as bis-N-maleimido-1,8-octane. Derivatizing agents such as methyl-3-[(p-azidophenyl)dithio]propioimidate yield photoactivatable intermediates that are capable of forming crosslinks in the presence of light. Alternatively, reactive water-insoluble matrices such as cyanogen bromide-activated carbohydrates and the reactive substrates described in U.S. Pat. Nos. 3,969,287; 3,691,016; 4,195,128; 4,247,642; 4,229,537; and 4,330,440 are employed for protein immobilization.
- Carbohydrate (oligosaccharide) groups may conveniently be attached to sites that are known to be glycosylation sites in proteins. Generally, O-linked oligosaccharides are attached to serine (Ser) or threonine (Thr) residues while N-linked oligosaccharides are attached to asparagine (Asn) residues when they are part of the sequence Asn-X-Ser/Thr, where X can be any amino acid except proline. X is preferably one of the 19 naturally occurring amino acids other than proline. The structures of N-linked and O-linked oligosaccharides and the sugar residues found in each type are different. One type of sugar that is commonly found on both is N-acetylneuraminic acid (referred to as sialic acid). Sialic acid is usually the terminal residue of both N-linked and O-linked oligosaccharides and, by virtue of its negative charge, may confer acidic properties to the glycosylated compound. Such site(s) may be incorporated in the linker of the compounds of this invention and are preferably glycosylated by a cell during recombinant production of the polypeptide compounds (e.g., in mammalian cells such as CHO, BHK, COS). However, such sites may further be glycosylated by synthetic or semi-synthetic procedures known in the art.
- Other possible modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, oxidation of the sulfur atom in Cys, methylation of the alpha-amino groups of lysine, arginine, and histidine side chains. Creighton,Proteins: Structure and Molecule Properties (W. H. Freeman & Co., San Francisco), pp. 79-86 (1983).
- Compounds of the present invention may be changed at the DNA level, as well. The DNA sequence of any portion of the compound may be -changed to codons more compatible with the chosen host cell. ForE. coli, which is the preferred host cell, optimized codons are known in the art.
- Codons may be substituted to eliminate restriction sites or to include silent restriction sites, which may aid in processing of the DNA in the selected host cell. The vehicle, linker and peptide DNA sequences may be modified to include any of the foregoing sequence changes.
- Methods of Making
- The compounds of this invention largely may be made in transformed host cells using recombinant DNA techniques. To do so, a recombinant DNA molecule coding for the peptide is prepared. Methods of preparing such DNA molecules are well known in the art. For instance, sequences coding for the peptides could be excised from DNA using suitable restriction enzymes. Alternatively, the DNA molecule could be synthesized using chemical synthesis techniques, such as the phosphoramidate method. Also, a combination of these techniques could be used.
- The invention also includes a vector capable of expressing the peptides in an appropriate host. The vector comprises the DNA molecule that codes for the peptides operatively linked to appropriate expression control sequences. Methods of effecting this operative linking, either before or after the DNA molecule is inserted into the vector, are well known. Expression control sequences include promoters, activators, enhancers, operators, ribosomal binding sites, start signals, stop signals, cap signals, polyadenylation signals, and other signals involved with the control of transcription or translation.
- The resulting vector having the DNA molecule thereon is used to transform an appropriate host. This transformation may be performed using methods well known in the art.
- Any of a large number of available and well-known host cells may be used in the practice of this invention. The selection of a particular host is dependent upon a number of factors recognized by the art. These include, for example, compatibility with the chosen expression vector, toxicity of the peptides encoded by the DNA molecule, rate of transformation, ease of recovery of the peptides, expression characteristics, bio-safety and costs. A balance of these factors must be struck with the understanding that not all hosts may be equally effective for the expression of a particular DNA sequence. Within these general guidelines, useful microbial hosts include bacteria (such asE. coli sp.), yeast (such as Saccharomyces sp.) and other fungi, insects, plants, mammalian (including human) cells in culture, or other hosts known in the art.
- Next, the transformed host is cultured and purified. Host cells may be cultured under conventional fermentation conditions so that the desired compounds are expressed. Such fermentation conditions are well known in the art. Finally, the peptides are purified from culture by methods well known in the art.
- The compounds may also be made by synthetic methods. For example, solid phase synthesis techniques may be used. Suitable techniques are well known in the art, and include those described in Merrifield (1973),Chem. Polypeptides, pp. 335-61 (Katsoyannis and Panayotis eds.); Merrifield (1963), J. Am. Chem. Soc. 85: 2149; Davis et al. (1985), Biochem. Intl. 10: 394-414; Stewart and Young (1969), Solid Phase Peptide Synthesis; U.S. Pat. No. 3,941,763; Finn et al. (1976), The Proteins (3rd ed.) 2: 105-253; and Erickson et al. (1976), The Proteins (3rd ed.)2: 257-527. Solid phase synthesis is the preferred technique of making individual peptides since it is the most cost-effective method of making small peptides.
- Compounds that contain derivatized peptides or which contain non-peptide groups may be synthesized by well-known organic chemistry techniques.
- Uses of the Compounds
- In general. The compounds of this invention have pharmacologic activity resulting from their ability to bind to proteins of interest as agonists, mimetics or antagonists of the native ligands of such proteins of interest. The utility of specific compounds is shown in Table 2. The activity of these compounds can be measured by assays known in the art. For the TPO-mimetic and EPO-mimetic compounds, in vivo assays are further described in the Examples section herein.
- In addition to therapeutic uses, the compounds of the present invention are useful in diagnosing diseases characterized by dysfunction of their associated protein of interest. In one embodiment, a method of detecting in a biological sample a protein of interest (e.g., a receptor) that is capable of being activated comprising the steps of: (a) contacting the sample with a compound of this invention; and (b) detecting activation of the protein of interest by the compound. The biological samples include tissue specimens, intact cells, or extracts thereof. The compounds of this invention may be used as part of a diagnostic kit to detect the presence of their associated proteins of interest in a biological sample. Such kits employ the compounds of the invention having an attached label to allow for detection. The compounds are useful for identifying normal or abnormal proteins of interest. For the EPO-mimetic compounds, for example, presence of abnormal protein of interest in a biological sample may be indicative of such disorders as Diamond Blackfan anemia, where it is believed that the EPO receptor is dysfunctional.
- Therapeutic uses of EPO-mimetic compounds. The EPO-mimetic compounds of the invention are useful for treating disorders characterized by low red blood cell levels. Included in the invention are methods of modulating the endogenous activity of an EPO receptor in a mammal, preferably methods of increasing the activity of an EPO receptor. In general, any condition treatable by erythropoietin, such as anemia, may also be treated by the EPO-mimetic compounds of the invention. These compounds are administered by an amount and route of delivery that is appropriate for the nature and severity of the condition being treated and may be ascertained by one skilled in the art. Preferably, administration is by injection, either subcutaneous, intramuscular, or intravenous.
- Therapeutic uses of TPO-mimetic compounds. For the TPO-mimetic compounds, one can utilize such standard assays as those described in WO95/26746 entitled “Compositions and Methods for Stimulating Megakaryocyte Growth and Differentiation”. In vivo assays also appear in the Examples hereinafter.
- The conditions to be treated are generally those that involve an existing megakaryocyte/platelet deficiency or an expected megakaryocyte/platelet deficiency (e.g., because of planned surgery or platelet donation). Such conditions will usually be the result of a deficiency (temporary or permanent) of active Mpl ligand in vivo. The generic term for platelet deficiency is thrombocytopenia, and hence the methods and compositions of the present invention are generally available for treating thrombocytopenia in patients in need thereof. Thrombocytopenia (platelet deficiencies) may be present for various reasons, including chemotherapy and other therapy with a variety of drugs, radiation therapy, surgery, accidental blood loss, and other specific disease conditions. Exemplary specific disease conditions that involve thrombocytopenia and may be treated in accordance with this invention are: aplastic anemia, idiopathic thrombocy openia, metastatic tumors which result in thrombocytopenia, systemic lupus erythematosus, splenomegaly, Fanconi's syndrome, vitamin B12 deficiency, folic acid deficiency, May-Hegglin anomaly, Wiskott-Aldrich syndrome, and paroxysmal nocturnal hemoglobinuria. Also, certain treatments for AIDS result in thrombocytopenia (e.g., AZT). Certain wound healing disorders might also benefit from an increase in platelet numbers.
- With regard to anticipated platelet deficiencies, e.g., due to future surgery, a compound of the present invention could be administered several days to several hours prior to the need for platelets. With regard to acute situations, e.g., accidental and massive blood loss, a compound of this invention could be administered along with blood or purified platelets.
- The TPO-mimetic compounds of this invention may also be useful in stimulating certain cell types other than megakaryocytes if such cells are found to express Mpl receptor. Conditions associated with such cells that express the Mpl receptor, which are responsive to stimulation by the Mpl ligand, are also within the scope of this invention.
- The TPO-mimetic compounds of this invention may be used in any situation in which production of platelets or platelet precursor cells is desired, or in which stimulation of the c-Mpl receptor is desired. Thus, for example, the compounds of this invention may be used to treat any condition in a mammal wherein there is a need of platelets, megakaryocytes, and the like. Such conditions are described in detail in the following exemplary sources: WO95/26746; WO95/21919; WO95/18858; WO95/21920 and are incorporated herein.
- The TPO-mimetic compounds of this invention may also be useful in maintaining the viability or storage life of platelets and/or megakaryocytes and related cells. Accordingly, it could be useful to include an effective amount of one or more such compounds in a composition containing such cells.
- The therapeutic methods, compositions and compounds of the present invention may also be employed, alone or in combination with other cytokines, soluble Mpl receptor, hematopoietic factors, interleukins, growth factors or antibodies in the treatment of disease states characterized by other symptoms as well as platelet deficiencies. It is anticipated that the inventive compound will prove useful in treating some forms of thrombocytopenia in combination with general stimulators of hematopoiesis, such as IL-3 or GM-CSF. Other megakaryocytic stimulatory factors, i.e., meg-CSF, stem cell factor (SCF), leukemia inhibitory factor (LIF), oncostatin M (OSM), or other molecules with megakaryocyte stimulating activity may also be employed with Mpl ligand. Additional exemplary cytokines or hematopoietic factors for such co-administration include IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-11, colony stimulating factor-1 (CSF-1), SCF, GM-CSF, granulocyte colony stimulating factor (G-CSF), EPO, interferon-alpha (IFN-alpha), consensus interferon, IFN-beta, or IFN-gamma. It may further be useful to administer, either simultaneously or sequentially, an effective amount of a soluble mammalian Mpl receptor, which appears to have an effect of causing megakaryocytes to fragment into platelets once the megakaryocytes have reached mature form. Thus, administration of an inventive compound (to enhance the number of mature megakaryocytes) followed by administration of the soluble Mpl receptor (to inactivate the ligand and allow the mature megakaryocytes to produce platelets) is expected to be a particularly effective means of stimulating platelet production. The dosage recited above would be adjusted to compensate for such additional components in the therapeutic composition. Progress of the treated patient can be monitored by conventional methods.
- In cases where the inventive compounds are added to compositions of platelets and/or megakaryocytes and related cells, the amount to be included will generally be ascertained experimentally by techniques and assays known in the art. An exemplary range of amounts is 0.1 μg-1 mg inventive compound per 106 cells.
- Pharmaceutical Compositions
- In General. The present invention also provides methods of using pharmaceutical compositions of the inventive compounds. Such pharmaceutical compositions may be for administration for injection, or for oral, pulmonary, nasal, transdermal or other forms of administration. In general, the invention encompasses pharmaceutical compositions comprising effective amounts of a compound of the invention together with pharmaceutically acceptable diluents, preservatives, solubilizers, emulsifiers, adjuvants and/or carriers. Such compositions include diluents of various buffer content (e.g., Tris-HCl, acetate, phosphate), pH and ionic strength; additives such as detergents and solubilizing agents (e.g., Tween 80, Polysorbate 80), anti-oxidants (e.g., ascorbic acid, sodium metabisulfite), preservatives (e.g., Thimersol, benzyl alcohol) and bulking substances (e.g., lactose, mannitol); incorporation of the material into particulate preparations of polymeric compounds such as polylactic acid, polyglycolic acid, etc. or into liposomes. Hyaluronic acid may also be used, and this may have the effect of promoting sustained duration in the circulation. Such compositions may influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the present proteins and derivatives. See, e.g., Remington's Pharmaceutical Sciences, 18th Ed. (1990, Mack Publishing Co., Easton, Pa. 18042) pages 1435-1712 which are herein incorporated by reference. The compositions may be prepared in liquid form, or may be in dried powder, such as lyophilized form. Implantable sustained release formulations are also contemplated, as are transdermal formulations.
- Oral dosage forms. Contemplated for use herein are oral solid dosage forms, which are described generally in Chapter 89 of Remington's Pharmaceutical Sciences (1990), 18th Ed., Mack Publishing Co. Easton Pa. 18042, which is herein incorporated by reference. Solid dosage forms include tablets, capsules, pills, troches or lozenges, cachets or pellets. Also, liposomal or proteinoid encapsulation may be used to formulate the present compositions (as, for example, proteinoid microspheres reported in U.S. Pat. No. 4,925,673). Liposomal encapsulation may be used and the liposomes may be derivatized with various polymers (e.g., U.S. Pat. No. 5,013,556). A description of possible solid dosage forms for the therapeutic is given in
Chapter 10 of Marshall, K., Modern Pharmaceutics (1979), edited by G. S. Banker and C. T. Rhodes, herein incorporated by reference. In general, the formulation will include the inventive compound, and inert ingredients which allow for protection against the stomach environment, and release of the biologically active material in the intestine. - Also specifically contemplated are oral dosage forms of the above inventive compounds. If necessary, the compounds may be chemically modified so that oral delivery is efficacious. Generally, the chemical modification contemplated is the attachment of at least one moiety to the compound molecule itself, where said moiety permits (a) inhibition of proteolysis; and (b) uptake into the blood stream from the stomach or intestine. Also desired is the increase in overall stability of the compound and increase in circulation time in the body. Moieties useful as covalently attached vehicles in this invention may also be used for this purpose.
- Examples of such moieties include: PEG, copolymers of ethylene glycol and propylene glycol, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone and polyproline. See, for example, Abuchowski and Davis,Soluble Polymer-Enzyme Adducts, Enzymes as Drugs (1981), Hocenberg and Roberts, eds., Wiley-Interscience, New York, N.Y., pp 367-83; Newmark, et al. (1982), J. Appl. Biochem. 4:185-9. Other polymers that could be used are poly-1,3-dioxolane and poly-1,3,6-tioxocane. Preferred for pharmaceutical usage, as indicated above, are PEG moieties.
- For oral delivery dosage forms, it is also possible to use a salt of a modified aliphatic amino acid, such as sodium N-(8-[2-hydroxybenzoyl]amino) caprylate (SNAC), as a carrier to enhance absorption of the therapeutic compounds of this invention. The clinical efficacy of a heparin formulation using SNAC has been demonstrated in a Phase II trial conducted by Emisphere Technologies. See U.S. Pat. No. 5,792,451, “Oral drug delivery composition and methods”.
- The compounds of this invention can be included in the formulation as fine multiparticulates in the form of granules or pellets of particle size about 1 mm. The formulation of the material for capsule administration could also be as a powder, lightly compressed plugs or even as tablets. The therapeutic could be prepared by compression.
- Colorants and flavoring agents may all be included. For example, the protein (or derivative) may be formulated (such as by liposome or microsphere encapsulation) and then further contained within an edible product, such as a refrigerated beverage containing colorants and flavoring agents.
- One may dilute or increase the volume of the compound of the invention with an inert material. These diluents could include carbohydrates, especially mannitol, α-lactose, anhydrous lactose, cellulose, sucrose, modified dextrans and starch. Certain inorganic salts may also be used as fillers including calcium triphosphate, magnesium carbonate and sodium chloride. Some commercially available diluents are Fast-Flo, Emdex, STA-
Rx 1500, Emcompress and Avicell. - Disintegrants may be included in the formulation of the therapeutic into a solid dosage form. Materials used as disintegrants include but are not limited to starch including the commercial disintegrant based on starch, Explotab. Sodium starch glycolate, Amberlite, sodium carboxymethylcellulose, ultramylopectin, sodium alginate, gelatin, orange peel, acid carboxymethyl cellulose, natural sponge and bentonite may all be used. Another form of the disintegrants are the insoluble cationic exchange resins. Powdered gums may be used as disintegrants and as binders and these can include powdered gums such as agar, Karaya or tragacanth. Alginic acid and its sodium salt are also useful as disintegrants.
- Binders may be used to hold the therapeutic agent together to form a hard tablet and include materials from natural products such as acacia, tragacanth, starch and gelatin. Others include methyl cellulose (MC), ethyl cellulose (EC) and carboxymethyl cellulose (CMC). Polyvinyl pyrrolidone (PVP) and hydroxypropylmethyl cellulose (HPMC) could both be used in alcoholic solutions to granulate the therapeutic.
- An antifrictional agent may be included in the formulation of the therapeutic to prevent sticking during the formulation process. Lubricants may be used as a layer between the therapeutic and the die wall, and these can include but are not limited to; stearic acid including its magnesium and calcium salts, polytetrafluoroethylene (PTFE), liquid paraffin, vegetable oils and waxes. Soluble lubricants may also be used such as sodium lauryl sulfate, magnesium lauryl sulfate, polyethylene glycol of various molecular weights,
Carbowax - Glidants that might improve the flow properties of the drug during formulation and to aid rearrangement during compression might be added. The glidants may include starch, talc, pyrogenic silica and hydrated silicoaluminate.
- To aid dissolution of the compound of this invention into the aqueous environment a surfactant might be added as a wetting agent. Surfactants may include anionic detergents such as sodium lauryl sulfate, dioctyl sodium sulfosuccinate and dioctyl sodium sulfonate. Cationic detergents might be used and could include benzalkonium chloride or benzethonium chloride. The list of potential nonionic detergents that could be included in the formulation as surfactants are lauromacrogol 400, polyoxyl 40 stearate, polyoxyethylene hydrogenated
castor oil polysorbate - Additives may also be included in the formulation to enhance uptake of the compound. Additives potentially having this property are for instance the fatty acids oleic acid, linoleic acid and linolenic acid.
- Controlled release formulation may be desirable. The compound of this invention could be incorporated into an inert matrix which permits release by either diffusion or leaching mechanisms e.g., gums. Slowly degenerating matrices may also be incorporated into the formulation, e.g., alginates, polysaccharides. Another form of a controlled release of the compounds of this invention is by a method based on the Oros therapeutic system (Alza Corp.), i.e., the drug is enclosed in a semipermeable membrane which allows water to enter and push drug out through a single small opening due to osmotic effects. Some enteric coatings also have a delayed release effect.
- Other coatings may be used for the formulation. These include a variety of sugars which could be applied in a coating pan. The therapeutic agent could also be given in a film coated tablet and the materials used in this instance are divided into 2 groups. The first are the nonenteric materials and include methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, methylhydroxy-ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl-methyl cellulose, sodium carboxy-methyl cellulose, providone and the polyethylene glycols. The second group consists of the enteric materials that are commonly esters of phthalic acid.
- A mix of materials might be used to provide the optimum film coating. Film coating may be carried out in a pan coater or in a fluidized bed or by compression coating.
- Pulmonary delivery forms. Also contemplated herein is pulmonary delivery of the present protein (or derivatives thereof). The protein (or derivative) is delivered to the lungs of a mammal while inhaling and traverses across the lung epithelial lining to the blood stream. (Other reports of this include Adjei et al.,Pharma. Res. (1990) 7: 565-9; Adjei et al. (1990), Internatl. J. Pharmaceutics 63: 135-44 (leuprolide acetate); Braquet et al. (1989), J. Cardiovasc. Pharmacol. 13 (suppl.5): s.143-146 (endothelin-1); Hubbard et al. (1989), Annals Int. Med. 3: 206-12 (α1-antitrypsin); Smith et al. (1989), J. Clin. Invest. 84:1145-6 (α1-proteinase); Oswein et al. (March 1990), “Aerosolization of Proteins”, Proc. Symp. Resp. Drug Delivery II, Keystone, Colo. (recombinant human growth hormone); Debs et al. (1988), J. Immunol. 140: 3482-8 (interferon-γ and tumor necrosis factor α) and Platz et al., U.S. Pat. No. 5,284,656 (granulocyte colony stimulating factor).
- Contemplated for use in the practice of this invention are a wide range of mechanical devices designed for pulmonary delivery of therapeutic products, including but not limited to nebulizers, metered dose inhalers, and powder inhalers, all of which are familiar to those skilled in the art. Some specific examples of commercially available devices suitable for the practice of this invention are the Ultravent nebulizer, manufactured by Mallinckrodt, Inc., St. Louis, Mo.; the Acorn II nebulizer, manufactured by Marquest Medical Products, Englewood, Colo.; the Ventolin metered dose inhaler, manufactured by Glaxo Inc., Research Triangle Park, North Carolina; and the Spinhaler powder inhaler, manufactured by Fisons Corp., Bedford, Mass.
- All such devices require the use of formulations suitable for the dispensing of the inventive compound. Typically, each formulation is specific to the type of device employed and may involve the use of an appropriate propellant material, in addition to diluents, adjuvants and/or carriers useful in therapy.
- The inventive compound should most advantageously be prepared in particulate form with an average particle size of less than 10 μm (or microns), most preferably 0.5 to 5 μm, for most effective delivery to the distal lung.
- Pharmaceutically acceptable carriers include carbohydrates such as trehalose, mannitol, xylitol, sucrose, lactose, and sorbitol. Other ingredients for use in formulations may include DPPC, DOPE, DSPC and DOPC. Natural or synthetic surfactants may be used. PEG may be used (even apart from its use in derivatizing the protein or analog). Dextrans, such as cyclodextran, may be used. Bile salts and other related enhancers may be used. Cellulose and cellulose derivatives may be used. Amino acids may be used, such as use in a buffer formulation.
- Also, the use of liposomes, microcapsules or microspheres, inclusion complexes, or other types of carriers is contemplated.
- Formulations suitable for use with a nebulizer, either jet or ultrasonic, will typically comprise the inventive compound dissolved in water at a concentration of about 0.1 to 25 mg of biologically active protein per mL of solution. The formulation may also include a buffer and a simple sugar (e.g., for protein stabilization and regulation of osmotic pressure). The nebulizer formulation may also contain a surfactant, to reduce or prevent surface induced aggregation of the protein caused by atomization of the solution in forming the aerosol.
- Formulations for use with a metered-dose inhaler device will generally comprise a finely divided powder containing the inventive compound suspended in a propellant with the aid of a surfactant. The propellant may be any conventional material employed for this purpose, such as a chlorofluorocarbon, a hydrochlorofluorocarbon, a hydrofluorocarbon, or a hydrocarbon, including trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethanol, and 1,1,1,2-tetrafluoroethane, or combinations thereof. Suitable surfactants include sorbitan trioleate and soya lecithin. Oleic acid may also be useful as a surfactant.
- Formulations for dispensing from a powder inhaler device will comprise a finely divided dry powder containing the inventive compound and may also include a bulking agent, such as lactose, sorbitol, sucrose, mannitol, trehalose, or xylitol in amounts which facilitate dispersal of the powder from the device, e.g., 50 to 90% by weight of the formulation.
- Nasal delivery forms. Nasal delivery of the inventive compound is also contemplated. Nasal delivery allows the passage of the protein to the blood stream directly after administering the therapeutic product to the nose, without the necessity for deposition of the product in the lung. Formulations for nasal delivery include those with dextran or cyclodextran. Delivery via transport across other mucous membranes is also contemplated.
- Dosages. The dosage regimen involved in a method for treating the above-described conditions will be determined by the attending physician, considering various factors which modify the action of drugs, e.g. the age, condition, body weight, sex and diet of the patient, the severity of any infection, time of administration and other clinical factors. Generally, the daily regimen should be in the range of 0.1-1000 micrograms of the inventive compound per kilogram of body weight, preferably 0.1-150 micrograms per kilogram.
- Specific Preferred Embodiments
- The inventors have determined preferred peptide sequences for molecules having many different kinds of activity. The inventors have further determined preferred structures of these preferred peptides combined with preferred linkers and vehicles. Preferred structures for these preferred peptides listed in Table 21 below.
TABLE 21 Preferred embodiments SEQ ID Sequence/structure NO: Activity F1-(G)5-IEGPTLRQWLAARA-(G)8-IEGPTLRQWLAARA 337 TPO-mimetic IEGPTLRQWLAARA-(G)8-IEGPTLRQWLAARA-(G)5-F1 338 TPO-mimetic F1-(G)5-IEGPTLRQWLAARA 1032 TPO-mimetic IEGPTLRQWLAARA-(G)5-F1 1033 TPO-mimetic F1-(G)5-GGTYSCHFGPLTWVCKPQGG-(G)4- 339 EPO-mimetic GGTYSCHFGPLTWVCKPQGG GGTYSCHFGPLTWVCKPQGG-(G)4- 340 EPO-mimetic GGTYSCHFGPLTWVCKPQGG-(G)5-F1 GGTYSCHFGPLTWVCKPQGG-(G)5-F1 1034 EPO-mimetic F1-(G)5-DFLPHYKNTSLGHRP 1045 TNF-α inhibitor DFLPHYKNTSLGHRP-(G)5-F1 1046 TNF-α inhibitor F1-(G)5-FEWTPGYWQPYALPL 1047 IL-1 R antagonist FEWTPGYWQPYALPL-(G)5-F1 1048 IL-1 R antagonist F1-(G)5-VEPNCDIHVMWEWECFERL 1049 VEGF-antagonist VEPNCDIHVMWEWECFERL-(G)5-F1 1050 VEGF-antagonist F1-(G)5-CTTHWGFTLC 1051 MMP inhibitor CTTHWGFTLC-(G)5-F1 1052 MMP inhibitor - The compounds described above may be prepared as described below. These examples comprise preferred embodiments of the invention and are illustrative rather than limiting.
- The following example uses peptides identified by the numbers appearing in Table A hereinafter.
- Preparation of
peptide 19.Peptide 17b (12 mg) and MeO-PEG-SH 5000 (30 mg, 2 equiv.) were dissolved in 1 ml aqueous buffer (pH 8). The mixture was incubated at RT for about 30 minutes and the reaction was checked by analytical HPLC, which showed a >80% completion of the reaction. The pegylated material was isolated by preparative HPLC. - Preparation of
peptide 20. Peptide 18 (14 mg) and MeO-PEG-maleimide (25 mg) were dissolved in about 1.5 ml aqueous buffer (pH 8). The mixture was incubated at RT for about 30 minutes, at which time about 70% transformation was complete as monitored with analytical HPLC by applying an aliquot of sample to the HPLC column. The pegylated material was purified by preparative HPLC. - Bioactivity assay. The TPO in vitro bioassay is a mitogenic assay utilizing an IL-3 dependent clone of murine 32D cells that have been transfected with human mpl receptor. This assay is described in greater detail in WO 95/26746. Cells are maintained in MEM medium containing 10% Fetal Clone II and 1 ng/ml mIL-3. Prior to sample addition, cells are prepared by rinsing twice with growth medium lacking mIL-3. An extended twelve point TPO standard curve is prepared, ranging from 33 to 39 μg/ml. Four dilutions, estimated to fall within the linear portion of the standard curve, (100 to 125 μg/ml), are prepared for each sample and run in triplicate. A volume of 100 μl of each dilution of sample or standard is added to appropriate wells of a 96 well microtiter plate -containing 10,000 cells/well. After forty-four hours at 37° C. and 10% CO2, MTS (a tetrazolium compound which is bioreduced by cells to a formazan) is added to each well. Approximately six hours later, the optical density is read on a plate reader at 490 nm. A dose response curve (log TPO concentration vs. O.D.—Background) is generated and linear regression analysis of points which fall in the linear portion of the standard curve is performed. Concentrations of unknown test samples are determined using the resulting linear equation and a correction for the dilution factor.
- TMP tandem repeats with polyglycine linkers. Our design of sequentially linked TMP repeats was based on the assumption that a dimeric form of TMP was required for its effective interaction with c-Mpl (the TPO receptor) and that depending on how they were wound up against each other in the receptor context, the two TMP molecules could be tethered together in the C- to N-terminus configuration in a way that would not perturb the global dimeric conformation. Clearly, the success of the design of tandem linked repeats depends on proper selection of the length and composition of the linker that joins the C- and N-termini of the two sequentially aligned TMP monomers. Since no structural information of the TMP bound to c-Mpl was available, a series of repeated peptides with linkers composed of 0 to 10 and 14 glycine residues (Table A) were synthesized. Glycine was chosen because of its simplicity and flexibility, based on the rationale that a flexible polyglycine peptide chain might allow for the free folding of the two tethered TMP repeats into the required conformation, while other amino acid sequences may adopt undesired secondary structures whose rigidity might disrupt the correct packing of the repeated peptide in the receptor context.
- The resulting peptides are readily accessible by conventional solid phase peptide synthesis methods (Merrifield (1963),J. Amer. Chem. Soc. 85: 2149) with either Fmoc or t-Boc chemistry. Unlike the synthesis of the C-terminally linked parallel dimer which required the use of an orthogonally protected lysine residue as the initial branch point to build the two peptide chains in a pseudosymmetrical way (Cwirla et al. (1997), Science 276: 1696-9), the synthesis of these tandem repeats was a straightforward, stepwise assembly of the continuous peptide chains from the C- to N-terminus. Since dimerization of TMP had a more dramatic effect on the proliferative activity than binding affinity as shown for the C-terminal dimer (Cwirla et al. (1997)), the synthetic peptides were tested directly for biological activity in a TPO-dependent cell-proliferation assay using an IL-3 dependent clone of murine 32D cells transfected with the full-length c-Mpl (Palacios et al., Cell 41:727 (1985)). As the test results showed, all the polyglycine linked tandem repeats demonstrated >1000 fold increases in potency as compared to the monomer, and were even more potent than the C-terminal dimer in this cell proliferation assay. The absolute activity of the C-terminal dimer in our assay was lower than that of the native TPO protein, which is different from the previously reported findings in which the C-terminal dimer was found to be as active as the natural ligand (Cwirla et al. (1997)). This might be due to differences in the conditions used in the two assays. Nevertheless, the difference in activity between tandem (C terminal of first monomer linked to N terminal of second monomer) and C-terminal (C terminal of first monomer linked to C terminal of second monomer; also referred to as parallel) dimers in the same assay clearly demonstrated the superiority of tandem repeat strategy over parallel peptide dimerization. It is interesting to note that a wide range of length is tolerated by the linker. The optimal linker between tandem peptides with the selected TMP monomers apparently is composed of 8 glycines.
- Other tandem repeats. Subsequent to this first series of TMP tandem repeats, several other molecules were designed either with different linkers or containing modifications within the monomer itself.
- The first of these molecules,
peptide 13, has a linker composed of GPNG, a sequence known to have a high propensity to form a β-turn-type secondary structure. Although still about 100-fold more potent than the monomer, this peptide was found to be >10-fold less active than the equivalent GGGG-linked analog. Thus, introduction of a relatively rigid β-turn at the linker region seemed to have caused a slight distortion of the optimal agonist conformation in this short linker form. - The Trp9 in the TMP sequence is a highly conserved residue among the active peptides isolated from random peptide libraries. There is also a highly conserved Trp in the consensus sequences of EPO mimetic peptides and this Trp residue was found to be involved in the formation of a hydrophobic core between the two EMPs and contributed to hydrophobic interactions with the EPO receptor. Livnah et al. (1996),Science 273: 464-71). By analogy, the Trp9 residue in TMP might have a similar function in dimerization of the peptide ligand, and as an attempt to modulate and estimate the effects of noncovalent hydrophobic forces exerted by the two indole rings, several analogs were made resulting from mutations at the Trp. So in
peptide 14, the Trp residue was replaced in each of the two TMP monomers with a Cys, and an intramolecular disulfide bond was formed between the two cysteines by oxidation which was envisioned to mimic the hydrophobic interactions between the two Trp residues in peptide dimerization.Peptide 15 is the reduced form ofpeptide 14. Inpeptide 16, the two Trp residues were replaced by Ala. As the assay data show, all three analogs were inactive. These data further demonstrated that Trp is critical for the activity of the TPO mimetic peptide, not just for dimer formation. - The next two peptides (peptide 17a, and 18) each contain in their 8-amino acid linker a Lys or Cys residue. These two compounds are precursors to the two PEGylated peptides (
peptide 19 and 20) in which the side chain of the Lys or Cys is modified by a PEG moiety. A PEG moiety was introduced at the middle of a relatively long linker, so that the large PEG component (5 kDa) is far enough away from the critical binding sites in the peptide molecule. PEG is a known biocompatible polymer which is increasingly used as a covalent modifier to improve the pharmacokinetic profiles of peptide- and protein-based therapeutics. - A modular, solution-based method was devised for convenient PEGylation of synthetic or recombinant peptides. The method is based on the now well established chemoselective ligation strategy which utilizes the specific reaction between a pair of mutually reactive functionalities. So, for
pegylated peptide 19, the lysine side chain was preactivated with a bromoacetyl group to givepeptide 17b to accommodate reaction with a thiol-derivatized PEG. To do that, an orthogonal protecting group, Dde, was employed for the protection of the lysine ε-amine. Once the whole peptide chain was assembled, the N-terminal amine was reprotected with t-Boc. Dde was then removed to allow for the bromoacetylation. This strategy gave a high quality crude peptide which was easily purified using conventional reverse phase HPLC. Ligation of the peptide with the thiol-modified PEG took place in aqueous buffer atpH 8 and the reaction completed within 30 minutes. MALDI-MS analysis of the purified, pegylated material revealed a characteristic, bell-shaped spectrum with an increment of 44 Da between the adjacent peaks. For PEG-peptide 20, a cysteine residue was placed in the linker region and its side chain thiol group would serve as an attachment site for a maleimide-containing PEG. - Similar conditions were used for the pegylation of this peptide. As the assay data revealed, these two pegylated peptides had even higher in vitro bioactivity as compared to their unpegylated counterparts.
-
Peptide 21 has in its 8-amino acid linker a potential glycosylation motif, NGS. Since our exemplary tandem repeats are made up of natural amino acids linked by peptide bonds, expression of such a molecule in an appropriate eukaryotic cell system should produce a glycopeptide with the carbohydrate moiety added on the side chain carboxyamide of Asn. Glycosylation is a common post-translational modification process which can have many positive impacts on the biological activity of a given protein by increasing its aqueous solubility and in vivo stability. As the assay data show, incorporation of this glycosylation motif into the linker maintained high bioactivity. The synthetic precursor of the potential glycopeptide had in effect an activity comparable to that of the -(G)8-linked analog. Once glycosylated, this peptide is expected to have the same order of activity as the pegylated peptides, because of the similar chemophysical properties exhibited by a PEG and a carbohydrate moiety. - The last peptide is a dimer of a tandem repeat. It was prepared by oxidizing
peptide 18, which formed an intermolecular disulfide bond between the two cysteine residues located at the linker. This peptide was designed to address the possibility that TMP was active as a tetramer. The assay data showed that this peptide was not more active than an average tandem repeat on an adjusted molar basis, which indirectly supports the idea that the active form of TMP is indeed a dimer, otherwise dimerization of a tandem repeat would have a further impact on the bioactivity. - In order to confirm the in vitro data in animals, one pegylated TMP tandem repeat (
compound 20 in Table A) was delivered subcutaneously to normal mice via osmotic pumps. Time and dose-dependent increases were seen in platelet numbers for the duration of treatment. Peak platelet levels over 4-fold baseline were seen onday 8. A dose of 10 μg/kg/day of the pegylated TMP repeat produced a similar response to rHuMGDF (non-pegylated) at 100 μg/kg/day delivered by the same route.TABLE A TPO-mimetic Peptides Peptide SEQ ID Relative No. Compound NO: Potency TPO ++++ TMP monomer 13 + TMP C-C dimer +++− TMP-(G)n-TMP: 1 n = 0 341 ++++− 2 n = 1 342 ++++ 3 n = 2 343 ++++ 4 n = 3 344 ++++ 5 n = 4 345 ++++ 6 n = 5 346 ++++ 7 n = 6 347 ++++ 8 n = 7 348 ++++ 9 n = 8 349 ++++− 10 n = 9 350 ++++ 11 n = 10 351 ++++ 12 n = 14 352 ++++ 13 TMP-GPNG-TMP 353 +++ 14 354 − 15 IEGPTLRQWCLAARA-GGGGGGGG- 355 − IEGPTLRQCLAARA-(linear) 16 IEGPTLRQALAARA-GGGGGGGG- 356 − IEGPTLRQALAARA 17a TMP-GGGKGGGG-TMP 357 ++++ 17b TMP-GGGK(BrAc)GGGG-TMP 358 ND 18 TMNP-GGGCGGGG-TMP 359 ++++ 19 TMP-GGGK(PEG)GGGG-TMP 360 +++++ 20 TMP-GGGC(PEG)GGGG-TMP 361 +++++ 21 TMP-GGGN*GSGG-TMP 362 ++++ 22 TMP-GGGCGGGG-TMP 363 | ++++ TMP-GGGCGGGG-TMP 363 - Discussion. It is well accepted that MGDF acts in a way similar to hGH, i.e., one molecule of the protein ligand binds two molecules of the receptor for its activation. Wells et al.(1996),Ann. Rev. Biochem. 65: 609-34. Now, this interaction is mimicked by the action of a much smaller peptide, TMP. However, the present studies suggest that this mimicry requires the concerted action of two TMP molecules, as covalent dimerization of TMP in either a C—C parallel or C—N sequential fashion increased the in vitro biological potency of the original monomer by a factor of greater than 103. The relatively low biopotency of the monomer is probably due to inefficient formation of the noncovalent dimer. A preformed covalent repeat has the ability to eliminate the entropy barrier for the formation of a noncovalent dimer which is exclusively driven by weak, noncovalent interactions between two molecules of the small, 14-residue peptide.
- It is intriguing that this tandem repeat approach had a similar effect on enhancing bioactivity as the reported C—C dimerization is intriguing. These two strategies brought about two very different molecular configurations. The C—C dimer is a quasi-symmetrical molecule, while the tandem repeats have no such symmetry in their linear structures. Despite this difference in their primary structures, these two types of molecules appeared able to fold effectively into a similar biologically active conformation and cause the dimerization and activation of c-Mpl. These experimental observations provide a number of insights into how the two TMP molecules may interact with one another in binding to c-Mpl. First, the two C-termini of the two bound TMP molecules must be in relatively close proximity with each other, as suggested by data on the C-terminal dimer. Second, the respective N- and C-termini of the two TMP molecules in the receptor complex must also be very closely aligned with each other, such that they can be directly tethered together with a single peptide bond to realize the near maximum activity-enhancing effect brought about by the tandem repeat strategy. Insertion of one or more (up to 14) glycine residues at the junction did not increase (or decrease) significantly the activity any further. This may be due to the fact that a flexible polyglycine peptide chain is able to loop out easily from the junction without causing any significant changes in the overall conformation. This flexibility seems to provide the freedom of orientation for the TMP peptide chains to fold into the required conformation in interacting with the receptor and validate it as a site of modification. Indirect evidence supporting this came from the study on
peptide 13, in which a much more rigid b-turn-forming sequence as the linker apparently forced a deviation of the backbone alignment around the linker which might have resulted in a slight distortion of the optimal conformation, thus resulting in a moderate (10-fold) decrease in activity as compared with the analogous compound with a 4-Gly linker. Third, Trp9 in TMP plays a similar role as Trp13 in EMP, which is involved not only in peptide:peptide interaction for the formation of dimers but also is important for contributing hydrophobic forces in peptide:receptor interaction. Results obtained with the W to C mutant analog,peptide 14, suggest that a covalent disulfide linkage is not sufficient to approximate the hydrophobic interactions provided by the Trp pair and that, being a short linkage, it might bring the two TMP monomers too close, therefore perturbing the overall conformation of the optimal dimeric structure. - An analysis of the possible secondary structure of the TMP peptide can provide further understanding on the interaction between TMP and c-Mpl. This can be facilitated by making reference to the reported structure of the EPO mimetic peptide. Livnah et al. (1996),Science 273:464-75 The receptor-bound EMP has a b-hairpin structure with a b-turn formed by the highly consensus Gly-Pro-Leu-Thr at the center of its sequence. Instead of GPLT, TMP has a highly selected GPTL sequence which is likely to form a similar turn. However, this turn-like motif is located near the N-terminal part in TMP. Secondary structure prediction using Chau-Fasman method suggests that the C-terminal half of the peptide has a tendency to adopt a helical conformation. Together with the highly conserved Trp at
position 9, this C-terminal helix may contribute to the stabilization of the dimeric structure. It is interesting to note that most of our tandem repeats are more potent than the C-terminal parallel dimer. Tandem repeats seem to give the molecule a better fit conformation than does the C—C parallel dimerization. The seemingly asymmetric feature of a tandem repeat might have brought it closer to the natural ligand which, as an asymmetric molecule, uses two different sites to bind two identical receptor molecules. - Introduction of a PEG moiety was envisaged to enhance the in vivo activity of the modified peptide by providing it a protection against proteolytic degradation and by slowing down its clearance through renal filtration. It was unexpected that pegylation could further increase the in vitro bioactivity of a tandem repeated TMP peptide in the cell-based proliferation assay.
- TMPs (and EMPs as described in Example 3) were expressed in either monomeric or dimeric form as either N-terminal or C-terminal fusions to the Fc region of human IgG1. In all cases, the expression construct utilized the luxPR promoter promoter in the plasmid expression vector pAMG21.
- Fc-TMP. A DNA sequence coding for the Fc region of human IgG1 fused in-frame to a monomer of the TPO-mimetic peptide was constructed using standard PCR technology. Templates for PCR reactions were the pFc-A3 vector and a synthetic TMP gene. The synthetic gene was constructed from the 3 overlapping oligonucleotides (SEQ ID NOS: 364, 365, and 366, respectively) shown below:
1842-97 AAA AAA GGA TCC TCG AGA TTA AGC ACG AGC AGC CAG CCA CTG ACG CAG AGT CGG ACC 1842-98 AAA GGT GGA GGT GGT GGT ATC GAA GGT CCG ACT CTG CGT 1842-99 CAG TGG CTG GCT GCT CGT GCT TAA TCT CGA GGA TCC TTT TTT - These oligonucleotides were annealed to form the duplex encoding an amino acid sequence (SEQ ID NOS: 367 and 368, respectively) shown below:
AAAGGTGGAGGTGGTGGTATCGAAGGTCCGACTCTGCGTCAGTGGCTGGCTGCTCGTGCT 1 ---------+---------+---------+---------+---------+---------+ 60 CCAGGCTGAGACGCAGTCACCGACCGACGAGCACGA a K G G G G G I E G P T L R Q W L A A R A − TAATCTCGAGGATCCTTTTTT 61 ---------+---------+- 81 ATTAGAGCTCCTAGGAAAAAA a * - This duplex was amplified in a PCR reaction using 1842-98 and 1842-97 as the sense and antisense primers.
- The Fc portion of the molecule was generated in a PCR reaction with pFc-A3 using the primers shown below (SEQ ID NOS: 369 and 370):
1216-52 AAC ATA AGT ACC TGT AGG ATC G 1830-51 TTCGATACCA CCACCTCCAC CTTTACCCGG AGACAGGGAG AGGCTCTTCTGC - The oligonucleotides 1830-51 and 1842-98 contain an overlap of 24 nucleotides, allowing the two genes to be fused together in the correct reading frame by combining the above PCR products in a third reaction using the outside primers, 1216-52 and 1842-97.
- The final PCR gene product (the full length fusion gene) was digested with restriction endonucleases XbaI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #3728.
- The nucleotide and amino acid sequences (SEQ ID NOS: 5 and 6) of the fusion protein are shown in FIG. 7.
- Fc-TMP-TMP. A DNA sequence coding for the Fc region of human IgG1 fused in-frame to a dimer of the TPO-mimetic peptide was constructed using standard PCR technology. Templates for PCR reactions were the pFc-A3 vector and a synthetic TMP-TMP gene. The synthetic gene was constructed from the 4 overlapping oligonucleotides (SEQ ID NOS: 371 to 374, respectively) shown below:
1830-52 AAA GGT GGA GGT GGT GGT ATC GAA GGT CCG ACT CTG CGT CAG TGG CTG GCT GCT CGT GCT 1830-53 ACC TCC ACC ACC AGC ACG AGC AGC CAG CCA CTG ACG CAG AGT CGG ACC 1830-54 GGT GGT GGA GGT GGC GGC GGA GGT ATT GAG GGC CCA ACC CTT CGC CAA TGG CTT GCA GCA CGC GCA 1830-55 AAA AAA AGG ATC CTC GAG ATT ATG CGC GTG CTG CAA GCC ATT GGC GAA GGG TTG GGC CCT CAA TAC CTC CGC CGC C - The 4 oligonucleotides were annealed to form the duplex encoding an amino acid sequence (SEQ ID NOS: 375 and 376, respectively) shown below:
AAAGGTGGAGGTGGTGGTATCGAAGGTCCGACTCTGCGTCAGTGGCTGGCTGCTCGTGCT 1 ---------+---------+---------+---------+---------+---------+ 60 CCAGGCTGAGACGCAGTCACCGACCGACGAGCACGA a K G G G G G I E G P T L R Q W L A A R A − GGTGGTGGAGGTGGCGGCGGAGGTATTGAGGGCCCAACCCTTCGCCAATGGCTTGCAGCA 61 ---------+---------+---------+---------+---------+---------+ 120 CCACCACCTCCACCGCCGCCTCCATAACTCCCGGGTTGGGAAGCGGTTACCGAACGTCGT a G G G G G G G G I E G P T L R Q W L A A − CGCGCA 121 ---------------------------148 GCGCGTATTAGAGCTCCTAGGAAAAAAA a R A *− - This duplex was amplified in a PCR reaction using 1830-52 and 1830-55 as the sense and antisense primers.
- The Fc portion of the molecule was generated in a PCR reaction with pFc-A3 using the primers 1216-52 and 1830-51 as described above for Fc-TMP. The full length fusion gene was obtained from a third PCR reaction using the outside primers 1216-52 and 1830-55.
- The final PCR gene product (the full length fusion gene) was digested with restriction endonucleases XbaI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described in example 1. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #3727.
- The nucleotide and amino acid sequences (SEQ ID NOS: 7 and 8) of the fusion protein are shown in FIG. 8.
- TMP-TMP-Fc. A DNA sequence coding for a tandem repeat of the TPO-mimetic peptide fused in-frame to the Fc region of human IgG1 was constructed using standard PCR technology. Templates for PCR reactions were the EMP-Fc plasmid from strain #3688 (see Example 3) and a synthetic gene encoding the TMP dimer. The synthetic gene for the tandem repeat was constructed from the 7 overlapping oligonucleotides shown below (SEQ ID NOS: 377 to 383, respectively):
1885-52 TTT TTT CAT ATG ATC GAA GGT CCG ACT CTG CGT CAG TGG 1885-53 AGC ACG AGC AGC CAG CCA CTG ACG CAG AGT CGG ACC TTC GAT CAT ATG 1885-54 CTG GCT GCT CGT GCT GGT GGA GGC GGT GGG GAC AAA ACT CAC ACA 1885-55 CTG GCT GCT CGT GCT GGC GGT GGT GGC GGA GGG GGT GGC ATT GAG GGC CCA 1885-56 AAG CCA TTG GCG AAG GGT TGG GCC CTC AAT GCC ACC CCC TCC GCC ACC ACC GCC 1885-57 ACC CTT CGC CAA TGG CTT GCA GCA CGC GCA GGG GGA GGC GGT GGG GAC AAA ACT 1885-58 CCC ACC GCC TCC CCC TGC GCG TGC TGC - These oligonucleotides were annealed to form the duplex shown encoding an amino acid sequence shown below (SEQ ID NOS 384 and 385):
TTTTTTCATATGATCGAAGGTCCGACTCTGCGTCAGTGGCTGGCTGCTCGTGCTGGCGGT 1 ---------+---------+---------+---------+---------+---------+ 60 GTATACTAGCTTCCAGGCTGAGACGCAGTCACCGACCGACGAGCACGACCGCCA a M I E G P T L R Q W L A A R A G G − GGTGGCGGAGGGGGTGGCATTGAGGGCCCAACCCTTCGCCAATGGCTGGCTGCTCGTGCT 61 ---------+---------+---------+---------+---------+---------+ 120 CCACCGCCTCCCCCACCGTAACTCCCGGGTTGGGAAGCGGTTACCGAACGTCGTGCGCGT a G G G G G G I E G P T L R Q W L A A R A − GGTGGAGGCGGTGGGGACAAAACTCTGGCTGCTCGTGCTGGTGGAGGCGGTGGGGACAAA 121 ---------+---------+---------+---------+---------+---------+ 180 CCCCCTCCGCCACCC a G G G G G D K T L A A R A G G G G G D K − ACTCACACA 181 --------- 189 a T H T − - This duplex was amplified in a PCR reaction using 1885-52 and 1885-58 as the sense and antisense primers.
- The Fc portion of the molecule was generated in a PCR reaction with DNA from the EMP-Fc fusion strain #3688 (see Example 3) using the primers 1885-54 and 1200-54. The full length fusion gene was obtained from a third PCR reaction using the outside primers 1885-52 and 1200-54.
- The final PCR gene product (the full length fusion gene) was digested with restriction endonucleases XbaI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for Fc-EMP herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #3798.
- The nucelotide and amino acid sequences (SEQ ID NOS: 9 and 10) of the fusion protein are shown in FIG. 9.
- TMP-Fc. A DNA sequence coding for a monomer of the TPO-mimetic peptide fused in-frame to the Fc region of human IgG1 was obtained fortuitously in the ligation in TMP-TMP-Fc, presumably due to the ability of primer 1885-54 to anneal to 1885-53 as well as to 1885-58. A single clone having the correct nucleotide sequence for the TMP-Fc construct was selected and designated Amgen strain #3788.
- The nucleotide and amino acid sequences (SEQ ID NOS: 11 and 12) of the fusion protein are shown in FIG. 10.
- Expression inE. coli. Cultures of each of the pAMG21-Fc-fusion constructs in E. coli GM221 were grown at 37° C. in Luria Broth medium containing 50 mg/ml kanamycin. Induction of gene product expression from the luxPR promoter was achieved following the addition of the synthetic autoinducer N-(3-oxohexanoyl)-DL-homoserine lactone to the culture media to a final concentration of 20 ng/ml. Cultures were incubated at 37° C. for a further 3 hours. After 3 hours, the bacterial cultures were examined by microscopy for the presence of inclusion bodies and were then collected by centrifugation. Refractile inclusion bodies were observed in induced cultures indicating that the Fc-fusions were most likely produced in the insoluble fraction in E. coli. Cell pellets were lysed directly by resuspension in Laemmli sample buffer containing 10% b-mercaptoethanol and were analyzed by SDS-PAGE. In each case, an intense coomassie-stained band of the appropriate molecular weight was observed on an SDS-PAGE gel.
- pAMG21. The expression plasmid pAMG21 can be derived from the Amgen expression vector pCFM1656 (ATCC #69576) which in turn be derived from the Amgen expression vector system described in U.S. Pat. No. 4,710,473. The pCFM1656 plasmid can be derived from the described pCFM836 plasmid (U.S. Pat. No. 4,710,473) by:
- (a) destroying the two endogenous NdeI restriction sites by end filling with T4 polymerase enzyme followed by blunt end ligation;
- (b) replacing the DNA sequence between the unique AatII and ClaI restriction sites containing the synthetic PL promoter with a similar fragment obtained from pCFM636 (U.S. Pat. No. 4,710,473) containing the PL promoter (see SEQ ID NO: 386 below); and
- (c) substituting the small DNA sequence between the unique ClaI and KpnI restriction sites with the oligonucleotide having the sequence of SEQ ID NO: 388.
Aat II 5′ CTAATTCCGCTCTCACCTACCAAACAATGCCCCCCTGCAAAAAATAAATTCATAT- SEQ ID NO: 386 3′ TGCAGATTAAGGCGAGAGTGGATGGTTTGTTACGGGGGGACGTTTTTTATTTAAGTATA- -AAAAAACATACAGATAACCATCTGCGGTGATAAATTATCTCTGGCGGTGTTGACATAAA- -TTTTTTGTATGTCTATTGGTAGACGCCACTATTTAATAGAGACCGCCACAACTGTATTT- - TACCACTGGCGGTGATACTGAGCACAT 3′:- ATGGTGACCGCCACTATGACTCGTGTAGC 5′Cla I 5′ CGATTTGATTCTAGAAGGAGGAATAACATATGGTTAACGCGTTGGAATTCGGTAC 3′:SEQ ID NO: 387 3′ TAAACTAAGATCTTCCTCCTTATTGTATACCAATTGCGCAACCTTAAGC 5′ClaI KpnI - The expression plasmid pAMG21 can then be derived from pCFM1656 by making a series of site-directed base changes by PCR overlapping oligo mutagenesis and DNA sequence substitutions. Starting with the BglII site (plasmid bp # 180) immediately 5′ to the plasmid replication promoter PcopB and proceeding toward the plasmid replication genes, the base pair changes are as shown in Table B below.
TABLE B Base pair changes resulting in pAMG21 pAMG21 bp # bp in pCFM1656 bp changed to in pAMG21 # 204 T/A C/G # 428 A/T G/C # 509 G/C A/T # 617 — insert two G/C bp # 679 G/C T/A # 980 T/A C/G # 994 G/C A/T # 1004 A/T C/G # 1007 C/G T/A # 1028 A/T T/A # 1047 C/G T/A # 1178 G/C T/A # 1466 G/C T/A # 2028 G/C bp deletion # 2187 C/G T/A # 2480 A/T T/A # 2499-2502 AGTG GTCA TCAC CAGT # 2642 TCCGAGC 7 bp deletion AGGCTCG # 3435 G/C A/T # 3446 G/C A/T # 3643 A/T T/A - The DNA sequence between the unique AatII (position #4364 in pCFM1656) and SacII (position #4585 in pCFM1656) restriction sites is substituted with the DNA sequence (SEQ ID NO: 23) shown in FIGS. 17A and 17B. During the ligation of the sticky ends of this substitution DNA sequence, the outside AatII and SacII sites are destroyed. There are unique AatII and SacII sites in the substituted DNA.
- GM221 (Amgen #2596). The Amgen host strain #2596 is anE. coli K-12 strain derived from Amgen strain #393. It has been modified to contain both the temperature sensitive lambda repressor cI857s7 in the early ebg region and the lacIq repressor in the late ebg region (68 minutes). The presence of these two repressor genes allows the use of this host with a variety of expression systems, however both of these repressors are irrelevant to the expression from luxPR. The untransformed host has no antibiotic resistances.
- The ribosome binding site of the cI857s7 gene has been modified to include an enhanced RBS. It has been inserted into the ebg operon between nucleotide position 1170 and 1411 as numbered in Genbank accession number M64441Gb_Ba with deletion of the intervening ebg sequence. The sequence of the insert is shown below with lower case letters representing the ebg sequences flanking the insert shown below
(SEQ ID NO: 388) ttattttcgtGCGGCCGCACCATTATCACCGCCAGAGGTAAACTAGTCAACACGCACGGTGTTAGATATTTAT CCCTTGCGGTGATAGATTGAGCACATCGATTTGATTCTAGAAGGAGGGATAATATATGAGCACAAAAAAGAAA CCATTAACACAAGAGCAGCTTGAGGACGCACGTCGCCTTAAAGCAATTTATGAAAAAAAGAAAAATGAACTTG GCTTATCCCAGGAATCTGTCGCAGACAAGATGGGGATGGGGCAGTCAGGCGTTGGTGCTTTATTTAATGGCAT CAATGCATTAAATGCTTATAACGCCGCATTGCTTACAAAAATTCTCAAAGTTAGCGTTGAAGAATTTAGCCCT TCAATCGCCAGAGAATCTACGAGATGTATGAAGCGGTTAGTATGCAGCCGTCACTTAGAAGTGAGTATGAGTA CCCTGTTTTTTCTCATGTTCAGGCAGGGATGTTCTCACCTAAGCTTAGAACCTTTACCAAAGGTGATGCGGAG AGATGGGTAAGCACAACCAAAAAAGCCAGTGATTCTGCATTCTGGCTTGAGGTTGAAGGTAATTCCATGACCG CACCAACAGGCTCCAAGCCAAGCTTTCCTGACGGAATGTTAATTCTCGTTGACCCTGAGCAGGCTGTTGAGCC AGGTGATTTCTGCATAGCCAGACTTGGGGGTGATGAGTTTACCTTCAAGAAACTGATCAGGGATAGCGGTCAG GTGTTTTTACAACCACTAAACCCACAGTACCCAATGATCCCATGCAATGAGAGTTGTTCCGTTGTGGGGAAAG TTATCGCTAGTCAGTGGCCTGAAGAGACGTTTGGCTGATAGACTAGTGGATCCACTAGTgtttctgccc: - The construct was delivered to the chromosome using a recombinant phage called MMebg-
cI857s7enhanced RBS # 4 into F′tet/393. After recombination and resolution only the chromosomal insert described above remains in the cell. It was renamed F′tet/GM101. F′tet/GM101 was then modified by the delivery of a lacIQ construct into the ebg operon between nucleotide position 2493 and 2937 as numbered in the Genbank accession number M64441Gb_Ba with the deletion of the intervening ebg sequence. The sequence of the insert is shown below with the lower case letters representing the ebg sequences flanking the insert (SEQ ID NO: 389) shown below:ggcggaaaccGACGTCCATCGAATGGTGCAAAACCTTTCGCGGTATGGCA TGATAGCGCCCGGAAGAGAGTCAATTCAGGGTGGTGAATGTGAAACCAGT AACGTTATACGATGTCGCAGAGTATGCCGGTGTCTCTTATCAGACCGTTT CCCGCGTGGTGAACCAGGCCAGCCACGTTTCTGCGAAAACGCGGGAAAAA GTCGAAGCGGCGATGGCGGAGCTGAATTACATTCCCAACCGCGTGGCACA ACAACTGGCGGGCAAACAGTCGCTCCTGATTGGCGTTGCCACCTCCAGTC TGGCCCTGCACGCGCCGTCGCAAATTGTCGCGGCGATTAAATCTCGCGCC GATCAACTGGGTGCCAGCGTGGTGGTGTCGATGGTAGAACGAAGCGGCGT CGAAGCCTGTAAAGCGGCGGTGCACAATCTTCTCGCGCAACGCGTCAGTG GGCTGATCATTAACTATCCGCTGGATGACCAGGATGCCATTGCTGTGGAA GCTGCCTGCACTAATGTTCCGGCGTTATTTCTTGATGTCTCTGACCAGAC ACCCATCAACAGTATTATTTTCTCCCATGAAGACGGTACGCGACTGGGCG TGGAGCATCTGGTCGCATTGGGTCACCAGCAAATCGCGCTGTTAGCGGGC CCATTAAGTTCTGTCTCGGCGCGTCTGCGTCTGGCTGGCTGGCATAAATA TCTCACTCGCAATCAAATTCAGCCGATAGCGGAACGGGAAGGCGACTGGA GTGCCATGTCCGGTTTTCAACAAACCATGCAAATGCTGAATGAGGGCATC GTTCCCACTGCGATGCTGGTTGCCAACGATCAGATGGCGCTGGGCGCAAT GCGCGCCATTACCGAGTCCGGGCTGCGCGTTGGTGCGGATATCTCGGTAG TGGGATACGACGATACCGAAGACAGCTCATGTTATATCCCGCCGTTAACC ACCATCAAACAGGATTTTCGCCTGCTGGGGCAAACCAGCGTGGACCGCTT GCTGCAACTCTCTCAGGGCCAGCCGGTGAAGGGCAATCAGCTGTTGCCCG TCTCACTGGTGAAAAGAAAAACCACCCTGGCGCCCAATACGCAAACCGCC TCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTC CCGACTGGAAAGCGGACAGTAAGGTACCATAGGATCCaggcacagga - The construct was delivered to the chromosome using a recombinant phage called AGebg-
LacIQ# 5 into F′tet/GM101. After recombination and resolution only the chromosomal insert described above remains in the cell. It was renamed F′tet/GM221. The F′tet episome was cured from the strain using acridine orange at a concentration of 25 μg/ml in LB. The cured strain was identified as tetracyline sensitive and was stored as GM221. - Expression. Cultures of pAMG21-Fc-TMP-TMP inE. coli GM221 in Luria Broth medium containing 50 μg/ml kanamycin were incubated at 37° C. prior to induction. Induction of Fc-TMP-TMP gene product expression from the luxPR promoter was achieved following the addition of the synthetic autoinducer N-(3-oxohexanoyl)-DL-homoserine lactone to the culture media to a final concentration of 20 ng/ml and cultures were incubated at 37° C. for a further 3 hours. After 3 hours, the bacterial cultures were examined by microscopy for the presence of inclusion bodies and were then collected by centrifugation. Refractile inclusion bodies were observed in induced cultures indicating that the Fc-TMP-TMP was most likely produced in the insoluble fraction in E. coli. Cell pellets were lysed directly by resuspension in Laemmli sample buffer containing 10% •-mercaptoethanol and were analyzed by SDS-PAGE. An intense Coomassie stained band of approximately 30 kDa was observed on an SDS-PAGE gel. The expected gene product would be 269 amino acids in length and have an expected molecular weight of about 29.5 kDa. Fermentation was also carried out under standard batch conditions at the 10 L scale, resulting in similar expression levels of the Fc-TMP-TMP to those obtained at bench scale.
- Purification of Fc-TMP-TMP. Cells are broken in water (1/10) by high pressure homogenization (2 passes at 14,000 PSI) and inclusion bodies are harvested by centrifugation (4200 RPM in J-6B for 1 hour). Inclusion bodies are solubilized in 6M guanidine, 50 mM Tris, 8 mM DTT, pH 8.7 for 1 hour at a 1/10 ratio. The solubilized mixture is diluted 20 times into 2M urea, 50 mM tris, 160 mM arginine, 3 mM cysteine, pH 8.5. The mixture is stirred overnight in the cold and then concentrated about 10 fold by ultafiltration. It is then diluted 3 fold with 10 mM Tris, 1.5M urea,
pH 9. The pH of this mixture is then adjusted topH 5 with acetic acid. The precipitate is removed by centrifugation and the supernatant is loaded onto a SP-Sepharose Fast Flow column equilibrated in 20 mM NaAc, 100 mM NaCl, pH 5(10 mg/ml protein load, room temperature). The protein is eluted off using a 20 column volume gradient in the same buffer ranging from 100 mM NaCl to 500 mM NaCl. The pool from the column is diluted 3 fold and loaded onto a SP-Sepharose HP column in 20 mM NaAc, 150 mM NaCl, pH 5(10 mg/ml protein load, room temperature). The protein is eluted off using a 20 column volume gradient in the same buffer ranging from 150 mM NaCl to 400 mM NaCl. The peak is pooled and filtered. - Characterization of Fc-TMP activity. The following is a summary of in vivo data in mice with various compounds of this invention.
- Mice: Normal female BDF1 approximately 10-12 weeks of age.
- Bleed schedule: Ten mice per group treated on
day 0, two groups started 4 days apart for a total of 20 mice per group. Five mice bled at each time point, mice were bled a minimum of three times a week. Mice were anesthetized with isoflurane and a total volume of 140-160 μl of blood was obtained by puncture of the orbital sinus. Blood was counted on a Technicon H1E blood analyzer running software for murine blood. Parameters measured were white blood cells, red blood cells, hematocrit, hemoglobin, platelets, neutrophils. - Treatments: Mice were either injected subcutaneously for a bolus treatment or implanted with 7-day micro-osmotic pumps for continuous delivery. Subcutaneous injections were delivered in a volume of 0.2 ml. Osmotic pumps were inserted into a subcutaneous incision made in the skin between the scapulae of anesthetized mice. Compounds were diluted in PBS with 0.1% BSA. All experiments included one control group, labeled “carrier” that were treated with this diluent only. The concentration of the test articles in the pumps was adjusted so that the calibrated flow rate from the pumps gave the treatment levels indicated in the graphs.
- Compounds: A dose titration of the compound was delivered to mice in 7 day micro-osmotic pumps. Mice were treated with various compounds at a single dose of 100 μg/kg in 7 day osmotic pumps. Some of the same compounds were then given to mice as a single bolus injection.
- Activity test results: The results of the activity experiments are shown in FIGS. 11 and 12. In dose response assays using 7-day micro-osmotic pumps, the maximum effect was seen with the compound of SEQ ID NO: 18 was at 100 μg/kg/day; the 10 μg/kg/day dose was about 50% maximally active and 1 μg/kg/day was the lowest dose at which activity could be seen in this assay system. The compound at 10 μg/kg/day dose was about equally active as 100 μg/kg/day unpegylated rHu-MGDF in the same experiment.
- Fc-EMP. A DNA sequence coding for the Fc region of human IgG1 fused in-frame to a monomer of the EPO-mimetic peptide was constructed using standard PCR technology. Templates for PCR reactions were a vector containing the Fc sequence (pFc-A3, described in International application WO 97/23614, published Jul. 3, 1997) and a synthetic gene encoding EPO monomer. The synthetic gene for the monomer was constructed from the 4 overlapping oligonucleotides (SEQ ID NOS: 390 to 393, respectively) shown below:
1798-2 TAT GAA AGG TGG AGG TGG TGG TGG AGG TAC TTA CTC TTG CCA CTT CGG CCC GCT GAC TTG G 1798-3 CGG TTT GCA AAC CCA AGT CAG CGG GCC GAA GTG GCA AGA GTA AGT ACC TCC ACC ACC ACC TCC ACC TTT CAT 1798-4 GTT TGC AAA CCG CAG GGT GGC GGC GGC GGC GGC GGT GGT ACC TAT TCC TGT CAT TTT 1798-5 CCA GGT CAG CGG GCC AAA ATG ACA GGA ATA GGT ACC ACC GCC GCC GCC GCC GCC ACC CTG - The 4 oligonucleotides were annealed to form the duplex encoding an amino acid sequence (SEQ ID NOS: 394 and 395, respectively) shown below:
TATGAAAGGTGGAGGTGGTGGTGGAGGTACTTACTCTTGCCACTTCGGCCCGCTGACTTG 1 ---------+---------+---------+---------+---------+---------+ 60 TACTTTCCACCTCCACCACCACCTCCATGAATGAGAACGGTGAAGCCGGGCGACTGAAC b M K G G G G G G G T Y S C H F G P L T W − GGTTTGCAAACCGCAGGGTGGCGGCGGCGGCGGCGGTGGTACCTATTCCTGTCATTTT 61 ---------+---------+---------+---------+---------+----------+----------+-- 133 CCAAACGTTTGGCGTCCCACCGCCGCCGCCGCCGCCACCATGGATAAGGACAGTAAAACCGGGCGACTGGACC b V C K P Q G G G G G G G G T Y S C H F − - This duplex was amplified in a PCR reaction using
1798-18 GCA GAA GAG CCT CTC CCT GTC TCC GGG TAA AGG TGG AGG TGG TGG TGG AGG TAC TTA CTC T and 1798-19 CTA ATT GGA TCC ACG AGA TTA ACC ACC CTG CGG TTT GCA A - as the sense and antisense primers (SEQ ID NOS: 396 and 397, respectively).
- The Fc portion of the molecule was generated in a PCR reaction with pFc-A3 using the primers
1216-52 AAC ATA AGT ACC TGT AGG ATC G 1798-17 AGA GTA AGT ACC TCC ACC ACC ACC TCC ACC TTT ACC CGG AGA CAG GGA GAG GCT CTT CTG C - which are SEQ ID NOS: 398 and 399, respectively. The oligonucleotides 1798-17 and 1798-18 contain an overlap of 61 nucleotides, allowing the two genes to be fused together in the correct reading frame by combining the above PCR products in a third reaction using the outside primers, 1216-52 and 1798-19.
- The final PCR gene product (the full length fusion gene) was digested with restriction endonucleases XbaI and BamHI, and then ligated into the vector pAMG21 (described below), also digested with XbaI and BamHI. Ligated DNA was transformed into competent host cells ofE. coli strain 2596 (GM221, described herein). Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #3718.
- The nucleotide and amino acid sequence of the resulting fusion protein (SEQ ID NOS: 15 and 16) are shown in FIG. 13.
- EMP-Fc. A DNA sequence coding for a monomer of the EPO-mimetic peptide fused in-frame to the Fc region of human IgG1 was constructed using standard PCR technology. Templates for PCR reactions were the pFC-A3a vector and a synthetic gene encoding EPO monomer. The synthetic gene for the monomer was constructed from the 4 overlapping oligonucleotides 1798-4 and 1798-5 (above) and 1798-6 and 1798-7 (SEQ ID NOS: 400 and 401, respectively) shown below:
1798-6 GGC CCG CTG ACC TGG GTA TGT AAG CCA CAA GGG GGT GGG GGA GGC GGG GGG TAA TCT CGA G 1798-7 GAT CCT CGA GAT TAC CCC CCG CCT CCC CCA CCC CCT TGT GGC TTA CAT AC - The 4 oligonucleotides were annealed to form the duplex encoding an amino acid sequence (SEQ ID NOS: 402 and 403, respectively) shown below:
GTTTGCAAACCGCAGGGTGGCGGCGGCGGCGGCGGTGGTACCTATTCCTGTCATTTTGGC 1 ---------+---------+---------+---------+---------+---------+ 60 GTCCCACCGCCGCCGCCGCCGCCACCATGGATAAGGACAGTAAAACCG A V C K P Q G G G G G G G G T Y S C H F G − CCGCTGACCTGGGTATGTAAGCCACAAGGGGGTGGGGGAGGCGGGGGGTAATCTCGAG 61 ---------+---------+---------+---------+---------+---------+- 122 GGCGACTGGACCCATACATTCGGTGTTCCCCCACCCCCTCCGCCCCCCATTAGAGCTCCTAG A P L T W V C K P Q G G G G G G G * - This duplex was amplified in a PCR reaction using
1798-21 TTA TTT CAT ATG AAA GGT GGT AAC TAT TCC TGT CAT TTT and 1798-22 TGG ACA TGT GTG AGT TTT GTC CCC CCC GCC TCC CCC ACC CCC T - as the sense and antisense primers (SEQ ID NOS: 404 and 405, respectively).
- The Fc portion of the molecule was generated in a PCR reaction with pFc-A3 using the primers
1798-23 AGG GGG TGG GGG AGG CGG GGG GGA CAA AAC TCA CAC ATG TCC A and 1200-54 GTT ATT GCT CAG CGG TGG CA - which are SEQ ID NOS: 406 and 407, respectively. The oligonucleotides 1798-22 and 1798-23 contain an overlap of 43 nucleotides allowing the two genes to be fused together in the correct reading frame by combining the above PCR products in a third reaction using the outside primers, 1787-21 and 1200-54.
- The final PCR gene product (the full length fusion gene) was digested with restriction endonucleases XbaI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described above. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #3688.
- The nucleotide and amino acid sequences (SEQ ID NOS: 17 and 18) of the resulting fusion protein are shown in FIG. 14.
- EMP-EMP-Fc. A DNA sequence coding for a dimer of the EPO-mimetic peptide fused in-frame to the Fc region of human IgG1 was constructed using standard PCR technology. Templates for PCR reactions were the EMP-Fc plasmid from strain #3688 above and a synthetic gene encoding the EPO dimer. The synthetic gene for the dimer was constructed from the 8 overlapping oligonucleotides (SEQ ID NOS:408 to 415, respectively) shown below:
1869-23 TTT TTT ATC GAT TTG ATT CTA GAT TTG AGT TTT AAC TTT TAG AAG GAG GAA TAA AAT ATG 1869-48 TAA AAG TTA AAA CTC AAA TCT AGA ATC AAA TCG ATA AAA AA 1871-72 GGA GGT ACT TAC TCT TGC CAC TTC GGC CCG CTG ACT TGG GTT TGC AAA CCG 1871-73 AGT CAG CGG GCC GAA GTG GCA AGA GTA AGT ACC TCC CAT ATT TTA TTC CTC CTT C 1871-74 CAG GGT GGC GGC GGC GGC GGC GGT GGT ACC TAT TCC TGT CAT TTT GGC CCG CTG ACC TGG 1871-75 AAA ATG ACA GGA ATA GGT ACC ACC GCC GCC GCC GCC GCC ACC CTG CGG TTT GCA AAC CCA 1871-78 GTA TGT AAG CCA CAA GGG GGT GGG GGA GGC GGG GGG GAC AAA ACT CAC ACA TGT CCA 1871-79 AGT TTT GTC CCC CCC GCC TCC CCC ACC CCC TTG TGG CTT ACA TAC CCA GGT CAG CGG GCC - The 8 oligonucleotides were annealed to form the duplex encoding an amino acid sequence (SEQ ID NOS: 416 and 417, respectively) shown below:
TTTTTTATCGATTTGATTCTAGATTTGAGTTTTAACTTTTAGAAGGAGGAATAAAATATG 1 ---------+---------+---------+---------+---------+---------+ 60 AAAAAATAGCTAAACTAAGATCTAAACTCAAAATTGAAAATCTTCCTCCTTATTTTATAC a M- − GGAGGTACTTACTCTTGCCACTTCGGCCCGCTGACTTGGGTTTGCAAACCGCAGGGTGGC 61 ---------+---------+---------+---------+---------+---------+ 120 CCTCCATGAATGAGAACGGTGAAGCCGGGCGACTGAACCCAAACGTTTGGCGTCCCACCG a G G T Y S C H F G P L T W V C K P Q G G − GGCGGCGGCGGCGGTGGTACCTATTCCTGTCATTTTGGCCCGCTGACCTGGGTATGTAAG 121 ---------+---------+---------+---------+---------+---------+ 180 CCGCCGCCGCCGCCACCATGGATAAGGACAGTAAAACCGGGCGACTGGACCCATACATTC a G G G G G G T Y S C H F G P L T W V C K − CCACAAGGGGGTGGGGGAGGCGGGGGGGACAAAACTCACACATGTCCA 181 ---------+---------+---------+---------+-------- 228 GGTGTTCCCCCACCCCCTCCGCCCCCCCTGTTTTGA a P Q G G G G G G G D K T H T C P − - This duplex was amplified in a PCR reaction using 1869-23 and 1871-79 (shown above) as the sense and antisense primers.
- The Fc portion of the molecule was generated in a PCR reaction with strain 3688 DNA using the primers 1798-23 and 1200-54 (shown above).
- The oligonucleotides 1871-79 and 1798-23 contain an overlap of 31 nucleotides, allowing the two genes to be fused together in the correct reading frame by combining the above PCR products in a third reaction using the outside primers, 1869-23 and 1200-54.
- The final PCR gene product (the full length fusion gene) was digested with restriction endonucleases XbaI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for Fc-EMP. Clones were screened for ability to produce the recombinant protein product and possession of the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #3813.
- The nucleotide and amino acid sequences (SEQ ID NOS: 19 and 20, respectively) of the resulting fusion protein are shown in FIG. 15. There is a silent mutation at position 145 (A to G, shown in boldface) such that the final construct has a different nucleotide sequence than the oligonucleotide 1871-72 from which it was derived.
- Fc-EMP-EMP. A DNA sequence coding for the Fc region of human IgG1 fused in-frame to a dimer of the EPO-mimetic peptide was constructed using standard PCR technology. Templates for PCR reactions were the plasmids from strains 3688 and 3813 above.
- The Fc portion of the molecule was generated in a PCR reaction with strain 3688 DNA using the primers 1216-52 and 1798-17 (shown above). The EMP dimer portion of the molecule was the product of a second PCR reaction with strain 3813 DNA using the primers 1798-18 (also shown above) and SEQ ID NO: 418, shown below:
- 1798-20 CTA ATT GGA TCC TCG AGA TTA ACC CCC TTG TGG CTT ACAT
- The oligonucleotides 1798-17 and 1798-18 contain an overlap of 61 nucleotides, allowing the two genes to be fused together in the correct reading frame by combining the above PCR products in a third reaction using the outside primers, 1216-52 and 1798-20.
- The final PCR gene product (the full length fusion gene) was digested with restriction endonucleases XbaI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for Fc-EMP. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #3822.
- The nucleotide and amino acid sequences (SEQ ID NOS: ______ and ______, respectively) of the fusion protein are shown in FIG. 16.
- Characterization of Fc-EMP activity. Characterization was carried out in vivo as follows.
- Mice: Normal female BDF1 approximately 10-12 weeks of age.
- Bleed schedule: Ten mice per group treated on
day 0, two groups started 4 days apart for a total of 20 mice per group. Five mice bled at each time point, mice were bled a maximum of three times a week. Mice were anesthetized with isoflurane and a total volume of 140-160 ml of blood was obtained by puncture of the orbital sinus. Blood was counted on a Technicon H1E blood analyzer running software for murine blood. Parameters measured were WBC, RBC, HCT, HGB, PLT, NEUT, LYMPH. - Treatments: Mice were either injected subcutaneously for a bolus treatment or implanted with 7 day micro-osmotic pumps for continuous delivery. Subcutaneous injections were delivered in a volume of 0.2 ml. Osmotic pumps were inserted into a subcutaneous incision made in the skin between the scapulae of anesthetized mice. Compounds were diluted in PBS with 0.1% BSA. All experiments included one control group, labeled “carrier” that were treated with this diluent only. The concentration of the test articles in the pumps was adjusted so that the calibrated flow rate from the pumps gave the treatment levels indicated in the graphs.
- Experiments: Various Fc-conjugated EPO mimetic peptides (EMPs) were delivered to mice as a single bolus injection at a dose of 100 μg/kg. Fc-EMPs were delivered to mice in 7-day micro-osmotic pumps. The pumps were not replaced at the end of 7 days. Mice were bled until day 51 when HGB and HCT returned to baseline levels.
- Fc-TNF-α inhibitors. A DNA sequence coding for the Fc region of human IgG1 fused in-frame to a monomer of the TNF-α inhibitory peptide was constructed using standard PCR technology. The Fc and 5 glycine linker portion of the molecule was generated in a PCR reaction with DNA from the Fc-EMP fusion strain #3718 (see Example 3) using the sense primer 1216-52 and the antisense primer 2295-89 (SEQ ID NOS: 1112 and 1113, respectively). The nucleotides encoding the TNF-α inhibitory peptide were provided by the PCR primer 2295-89 shown below:
1216-52 AAC ATA AGT ACC TGT AGG ATC G 2295-89 CCG CGG ATC CAT TAC GGA CGG TGA CCC AGA GAG GTG TTT TTG TAG TGC GGC AGG AAG TCA CCA CCA CCT CCA CCT TTA CCC - The oligonucleotide 2295-89 overlaps the glycine linker and Fc portion of the template by 22 nucleotides, with the PCR resulting in the two genes being fused together in the correct reading frame.
- The PCR gene product (the full length fusion gene) was digested with restriction endonucleases NdeI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #4544.
- The nucleotide and amino acid sequences (SEQ ID NOS: 1055 and 1056) of the fusion protein are shown in FIGS. 19A and 19B.
- TNF-α inhibitor-Fc. A DNA sequence coding for a TNF-α inhibitory peptide fused in-frame to the Fc region of human IgG1 was constructed using standard PCR technology. The template for the PCR reaction was a plasmid containing an unrelated peptide fused via a five glycine linker to Fc. The nucleotides encoding the TNF-α inhibitory peptide were provided by the sense PCR primer 2295-88, with primer 1200-54 serving as the antisense primer (SEQ ID NOS: 1117 and 407, respectively). The primer sequences are shown below:
2295-88 GAA TAA CAT ATG GAC TTC CTG CCG CAC TAC AAA AAC ACC TCT CTG GGT CAC CGT CCG GGT GGA GGC GGT GGG GAC AAA ACT 1200-54 GTT ATT GCT CAG CGG TGG CA - The oligonucleotide 2295-88 overlaps the glycine linker and Fc portion of the template by 24 nucleotides, with the PCR resulting in the two genes being fused together in the correct reading frame.
- The PCR gene product (the full length fusion gene) was digested with restriction endonucleases NdeI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #4543.
- The nucleotide and amino acid sequences (SEQ ID NOS: 1057 and 1058) of the fusion protein are shown in FIGS. 20A and 20B.
- Expression inE. coli. Cultures of each of the pAMG21-Fc-fusion constructs in E. coli GM221 were grown at 37° C. in Luria Broth medium containing 50 mg/ml kanamycin. Induction of gene product expression from the luxPR promoter was achieved following the addition of the synthetic autoinducer N-(3-oxohexanoyl)-DL-homoserine lactone to the culture media to a final concentration of 20 ng/ml. Cultures were incubated at 37° C. for a further 3 hours. After 3 hours, the bacterial cultures were examined by microscopy for the presence of inclusion bodies and were then collected by centrifugation. Refractile inclusion bodies were observed in induced cultures indicating that the Fc-fusions were most likely produced in the insoluble fraction in E. coli. Cell pellets were lysed directly by resuspension in Laemmli sample buffer containing 10% β-mercaptoethanol and were analyzed by SDS-PAGE. In each case, an intense coomassie-stained band of the appropriate molecular weight was observed on an SDS-PAGE gel.
- Purification of Fc-peptide fusion proteins. Cells are broken in water ({fraction (1/10)}) by high pressure homogenization (2 passes at 14,000 PSI) and inclusion bodies are harvested by centrifugation (4200 RPM in J-6B for 1 hour). Inclusion bodies are solubilized in 6M guanidine, 50 mM Tris, 8 mM DTT, pH 8.7 for 1 hour at a {fraction (1/10)} ratio. The solubilized mixture is diluted 20 times into 2M urea, 50 mM tris, 160 mM arginine, 3 mM cysteine, pH 8.5. The mixture is stirred overnight in the cold and then concentrated about 10 fold by ultafiltration. It is then diluted 3 fold with 10 mM Tris, 1.5M urea,
pH 9. The pH of this mixture is then adjusted topH 5 with acetic acid. The precipitate is removed by centrifugation and the supernatant is loaded onto a SP-Sepharose Fast Flow column equilibrated in 20 mM NaAc, 100 mM NaCl, pH 5 (10 mg/ml protein load, room temperature). The protein is eluted from the column using a 20 column volume gradient in the same buffer ranging from 100 mM NaCl to 500 mM NaCl. The pool from the column is diluted 3 fold and loaded onto a SP-Sepharose HP column in 20 mM NaAc, 150 mM NaCl, pH 5(10 mg/ml protein load, room temperature). The protein is eluted using a 20 column volume gradient in the same buffer ranging from 150 mM NaCl to 400 mM NaCl. The peak is pooled and filtered. - Characterization of activity of Fc-TNF-α inhibitor and TNF-α inhibitor-Fc. Binding of these peptide fusion proteins to TNF-(x can be characterized by BIAcore by methods available to one of ordinary skill in the art who is armed with the teachings of the present specification.
- Fc-IL-1 antagonist. A DNA sequence coding for the Fc region of human IgG1 fused in-frame to a monomer of an IL-1 antagonist peptide was constructed using standard PCR technology. The Fc and 5 glycine linker portion of the molecule was generated in a PCR reaction with DNA from the Fc-EMP fusion strain #3718 (see Example 3) using the sense primer 1216-52 and the antisense primer 2269-70 (SEQ ID NOS: 1112 and 1118, respectively). The nucleotides encoding the IL-1 antagonist peptide were provided by the PCR primer 2269-70 shown below:
1216-52 AAC ATA AGT ACC TGT AGG ATC G 2269-70 CCG CGG ATC CAT TAC AGC GGC AGA GCG TAC GGC TGC CAG TAA CCC GGG GTC CAT TCG AAA CCA CCA CCT CCA CCT TTA CCC - The oligonucleotide 2269-70 overlaps the glycine linker and Fc portion of the template by 22 nucleotides, with the PCR resulting in the two genes being fused together in the correct reading frame.
- The PCR gene product (the full length fusion gene) was digested with restriction endonucleases NdeI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #4506.
- The nucleotide and amino acid sequences (SEQ ID NOS: 1059 and 1060) of the fusion protein are shown in FIGS. 21A and 21B.
- IL-1 antagonist-Fc. A DNA sequence coding for an IL-1 antagonist peptide fused in-frame to the Fc region of human IgG1 was constructed using standard PCR technology. The template for the PCR reaction was a plasmid containing an unrelated peptide fused via a five glycine linker to Fc. The nucleotides encoding the IL-1 antagonist peptide were provided by the sense PCR primer 2269-69, with primer 1200-54 serving as the antisense primer (SEQ ID NOS: 1119 and 407, respectively). The primer sequences are shown below:
2269-69 GAA TAA CAT ATG TTC GAA TGG ACC CCG GGT TAC TGG CAG CCG TAC GCT CTG CCG CTG GGT GGA GGC GGT GGG GAC AAA ACT 1200-54 GTT ATT GCT CAG CGG TGG CA - The oligonucleotide 2269-69 overlaps the glycine linker and Fc portion of the template by 24 nucleotides, with the PCR resulting in the two
genes 35 being fused together in the correct reading frame. - The PCR gene product (the full length fusion gene) was digested with restriction endonucleases NdeI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #4505.
- The nucleotide and amino acid sequences (SEQ ID NOS: 1061 and 1062) of the fusion protein are shown in FIGS. 22A and 22B. Expression and purification were carried out as in previous examples.
- Characterization of Fc-IL-1 antagonist peptide and IL-1 antagonist peptide-Fc activity. IL-1 Receptor Binding competition between IL-1β, IL-1RA and Fc-conjugated IL-1 peptide sequences was carried out using the IGEN system. Reactions contained 0.4 nM biotin-IL-1R+15 nM IL-1-TAG+3 uM competitor+20 ug/ml streptavidin-conjugate beads, where competitors were IL-1RA, Fc-IL-1 antagonist, IL-1 antagonist-Fc). Competition was assayed over a range of competitor concentrations from 3 uM to 1.5 pM. The results are shown in Table C below:
TABLE C Results from IL-1 Receptor Binding Competition Assay IL-1pep-Fc Fc-IL-1pep IL-1ra KI 281.5 59.58 1.405 EC50 530.0 112.2 2.645 95% Confidence Intervals EC50 280.2 to 1002 54.75 to 229.8 1.149 to 6.086 KI 148.9 to 532.5 29.08 to 122.1 0.6106 to 3.233 Goodness of Fit R2 0.9790 0.9687 0.9602 - Fc-VEGF Antagonist. A DNA sequence coding for the Fc region of human IgG1 fused in-frame to a monomer of the VEGF mimetic peptide was constructed using standard PCR technology. The templates for the PCR reaction were the pFc-A3 plasmid and a synthetic VEGF mimetic peptide gene. The synthetic gene was assembled by annealing the following two oligonucleotides primer (SEQ ID NOS: 1120 and 1121, respectively):
2293-11 GTT GAA CCG AAC TGT GAC ATC CAT GTT ATG TGG GAA TGG GAA TGT TTT GAA CGT CTG 2293-12 CAG ACG TTC AAA ACA TTC CCA TTC CCA CAT AAC ATG GAT GTC ACA GTT CGG TTC AAC - The two oligonucleotides anneal to form the following duplex encoding an amino acid sequence shown below (SEQ ID NOS 1122):
GTTGAACCGAACTGTGACATCCATGTTATGTGGGAATGGGAATGTTTTGAACGTCTG 1 ---------+---------+---------+---------+---------+------- 57 CAACTTGGCTTGACACTGTAGGTACAATACACCCTTACCCTTACAAAACTTGCAGAC a V E P N C D I H V M W E W E C F E R L − - This duplex was amplified in a PCR reaction using 2293-05 and 2293-06 as the sense and antisense primers (SEQ ID NOS. 1125 and 1126).
- The Fc portion of the molecule was generated in a PCR reaction with the pFc-A3 plasmid using the primers 2293-03 and 2293-04 as the sense and antisense primers (SEQ ID NOS. 1123 and 1124, respectively). The full length fusion gene was obtained from a third PCR reaction using the outside primers 2293-03 and 2293-06. These primers are shown below:
2293-03 ATT TGA TTC TAG AAG GAG GAA TAA CAT ATG GAC AAA ACT CAC ACA TGT 2293-04 GTC ACA GTT CGG TTC AAC ACC ACC ACC ACC ACC TTT ACC CGG AGA CAG GGA 2293-05 TCC CTG TCT CCG GGT AAA GGT GGT GGT GGT GGT GTT GAA CCG AAC TGT GAC ATC 2293-06 CCG CGG ATC CTC GAG TTA CAG ACG TTC AAA ACA TTC CCA - The PCR gene product (the full length fusion gene) was digested with restriction endonucleases NdeI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #4523.
- The nucleotide and amino acid sequences (SEQ ID NOS: 1063 and 1064) of the fusion protein are shown in FIGS. 23A and 23B.
- VEGF antagonist-Fc. A DNA sequence coding for a VEGF mimetic peptide fused in-frame to the Fc region of human IgG1 was constructed using standard PCR technology. The templates for the PCR reaction were the pFc-A3 plasmid and the synthetic VEGF mimetic peptide gene described above. The synthetic duplex was amplified in a PCR reaction using 2293-07 and 2293-08 as the sense and antisense primers (SEQ ID NOS. 1127 and 1128, respectively).
- The Fc portion of the molecule was generated in a PCR reaction with the pFc-A3 plasmid using the primers 2293-09 and 2293-10 as the sense and antisense primers (SEQ ID NOS. 1129 and 1130, respectively). The full length fusion gene was obtained from a third PCR reaction using the outside primers 2293-07 and 2293-10. These primers are shown below:
2293-07 ATT TGA TTC TAG AAG GAG GAA TAA CAT ATG GTT GAA CCG AAC TGT GAC 2293-08 ACA TGT GTG AGT TTT GTC ACC ACC ACC ACC ACC CAG ACG TTC AAA ACA TTC 2293-09 GAA TGT TTT GAA CGT CTG GGT GGT GGT GGT GGT GAC AAA ACT CAC ACA TGT 2293-10 CCG CGG ATC CTC GAG TTA TTT ACC CGG AGA CAG GGA GAG - The PCR gene product (the full length fusion gene) was digested with restriction endonucleases NdeI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #4524.
- The nucleotide and amino acid sequences (SEQ ID NOS: 1065 and 1066) of the fusion protein are shown in FIGS. 24A and 24B. Expression and purification were carried out as in previous examples.
- Fc-MMP inhibitor. A DNA sequence coding for the Fc region of human IgG1 fused in-frame to a monomer of an MMP inhibitory peptide was constructed using standard PCR technology. The Fc and 5 glycine linker portion of the molecule was generated in a PCR reaction with DNA from the Fc-TNF-α inhibitor fusion strain #4544 (see Example 4) using the sense primer 1216-52 and the antisense primer 2308-67 (SEQ ID NOS: 1112 and 1131, respectively). The nucleotides encoding the MMP inhibitor peptide were provided by the PCR primer 2308-67 shown below:
1216-52 AAC ATA AGT ACC TGT AGG ATC G 2308-67 CCG CGG ATC CAT TAG CAC AGG GTG AAA CCC CAG TGG GTG GTG CAA CCA CCA CCT CCA CCT TTA CCC - The oligonucleotide 2308-67 overlaps the glycine linker and Fc portion of the template by 22 nucleotides, with the PCR resulting in the two genes being fused together in the correct reading frame.
- The PCR gene product (the full length fusion gene) was digested with restriction endonucleases NdeI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #4597.
- The nucleotide and amino acid sequences (SEQ ID NOS: 1067 and 1068) of the fusion protein are shown in FIGS. 25A and 25B. Expression and purification were carried out as in previous examples.
- MMP Inhibitor-Fc. A DNA sequence coding for an MMP inhibitory peptide fused in-frame to the Fc region of human IgG1 was constructed using standard PCR technology. The Fc and 5 glycine linker portion of the molecule was generated in a PCR reaction with DNA from the Fc-TNF-α inhibitor fusion strain #4543 (see Example 4). The nucleotides encoding the MMP inhibitory peptide were provided by the sense PCR primer 2308-66, with primer 1200-54 serving as the antisense primer (SEQ ID NOS: 1132 and 407, respectively). The primer sequences are shown below:
2308-66 GAA TAA CAT ATG TGC ACC ACC CAC TGG GGT TTC ACC CTG TGC GGT GGA GGC GGT GGG GAC AAA 1200-54 GTT ATT GCT CAG CGG TGG CA - The oligonucleotide 2269-69 overlaps the glycine linker and Fc portion of the template by 24 nucleotides, with the PCR resulting in the two genes being fused together in the correct reading frame.
- The PCR gene product (the full length fusion gene) was digested with restriction endonucleases NdeI and BamHI, and then ligated into the vector pAMG21 and transformed into competentE. coli strain 2596 cells as described for EMP-Fc herein. Clones were screened for the ability to produce the recombinant protein product and to possess the gene fusion having the correct nucleotide sequence. A single such clone was selected and designated Amgen strain #4598.
- The nucleotide and amino acid sequences (SEQ ID NOS: 1069 and 1070) of the fusion protein are shown in FIGS. 26A and 26B.
- The invention now being fully described, it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto, without departing from the spirit and scope of the invention as set forth herein.
- Abbreviations used throughout this specification are as defined below, unless otherwise defined in specific circumstances.
Ac acetyl (used to refer to acetylated residues) AcBpa acetylated p-benzoyl-L-phenylalanine ADCC antibody-dependent cellular cytotoxicity Aib aminoisobutyric acid bA beta-alanine Bpa p-benzoyl-L-phenylalanine BrAc bromoacetyl (BrCH2C(O) BSA Bovine serum albumin Bzl Benzyl Cap Caproic acid CTL Cytotoxic T lymphocytes CTLA4 Cytotoxic T lymphocyte antigen 4 DARC Duffy blood group antigen receptor DCC Dicylcohexylcarbodiimide Dde 1-(4,4-dimethyl-2,6-dioxo-cyclohexylidene)ethyl EMP Erythropoietin-mimetic peptide ESI-MS Electron spray ionization mass spectrometry EPO Erythropoietin Fmoc fluorenylmethoxycarbonyl G-CSF Granulocyte colony stimulating factor GH Growth hormone HCT hematocrit HGB hemoglobin hGH Human growth hormone HOBt 1-Hydroxybenzotriazole HPLC high performance liquid chromatography IL interleukin IL-R interleukin receptor IL-1R interleukin-1 receptor IL-1ra interleukin-1 receptor antagonist Lau Lauric acid LPS lipopolysaccharide LYMPH lymphocytes MALDI-MS Matrix-assisted laser desorption ionization mass spectrometry Me methyl MeO methoxy MHC major histocompatibility complex MMP matrix metalloproteinase MMPI matrix metalloproteinase inhibitor 1-Nap 1-napthylalanine NEUT neutrophils NGF nerve growth factor Nle norleucine NMP N-methyl-2-pyrrolidinone PAGE polyacrylamide gel electrophoresis PBS Phosphate-buffered saline Pbf 2,2,4,6,7-pendamethyldihydrobenzofuran-5-sulfonyl PCR polymerase chain reaction Pec pipecolic acid PEG Poly(ethylene glycol) pGlu pyroglutamic acid Pic picolinic acid PLT platelets pY phosphotyrosine RBC red blood cells RBS ribosome binding site RT room temperature (25° C.) Sar sarcosine SDS sodium dodecyl sulfate STK serine-threonine kinases t-Boc tert-Butoxycarbonyl tBu tert-Butyl TGF tissue growth factor THF thymic humoral factor TK tyrosine kinase TMP Thrombopoietin-mimetic peptide TNF Tissue necrosis factor TPO Thrombopoietin TRAIL TNF-related apoptosis-inducing ligand Trt trityl UK urokinase UKR urokinase receptor VEGF vascular endothelial cell growth factor VIP vasoactive intestinal peptide WBC white blood cells -
-
0 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 1133 <210> SEQ ID NO 1 <211> LENGTH: 684 <212> TYPE: DNA <213> ORGANISM: HUMAN <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)..(684) <223> OTHER INFORMATION: <400> SEQUENCE: 1 atg gac aaa act cac aca tgt cca cct tgt cca gct ccg gaa ctc ctg 48 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 ggg gga ccg tca gtc ttc ctc ttc ccc cca aaa ccc aag gac acc ctc 96 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 atg atc tcc cgg acc cct gag gtc aca tgc gtg gtg gtg gac gtg agc 144 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg gag 192 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 gtg cat aat gcc aag aca aag ccg cgg gag gag cag tac aac agc acg 240 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg aat 288 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc ccc 336 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca cag 384 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 gtg tac acc ctg ccc cca tcc cgg gat gag ctg acc aag aac cag gtc 432 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc gtg 480 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 gag tgg gag agc aat ggg cag ccg gag aac aac tac aag acc acg cct 528 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc acc 576 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 gtg gac aag agc agg tgg cag cag ggg aac gtc ttc tca tgc tcc gtg 624 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 atg cat gag gct ctg cac aac cac tac acg cag aag agc ctc tcc ctg 672 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 tct ccg ggt aaa 684 Ser Pro Gly Lys 225 <210> SEQ ID NO 2 <211> LENGTH: 228 <212> TYPE: PRT <213> ORGANISM: HUMAN <400> SEQUENCE: 2 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys 225 <210> SEQ ID NO 3 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SYNTHETIC SCHEME FOR PREPARATION OF PEGYLATED PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18)..(18) <223> OTHER INFORMATION: Methoxy-polyethylene glycol (5000 Dalton)-sulfoacetyl group attached to the sidechain. <400> SEQUENCE: 3 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Lys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 4 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SYNTHETIC SCHEME FOR PREPARATION OF PEGYLATED PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18)..(18) <223> OTHER INFORMATION: Methoxy-polyethylene glycol (5000 Dalton)-succinimidyl group attached to the sidechain. <400> SEQUENCE: 4 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Cys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 5 <211> LENGTH: 794 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (39)..(779) <223> OTHER INFORMATION: <400> SEQUENCE: 5 tctagatttg ttttaactaa ttaaaggagg aataacat atg gac aaa act cac aca 56 Met Asp Lys Thr His Thr 1 5 tgt cca cct tgt cca gct ccg gaa ctc ctg ggg gga ccg tca gtc ttc 104 Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 10 15 20 ctc ttc ccc cca aaa ccc aag gac acc ctc atg atc tcc cgg acc cct 152 Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 25 30 35 gag gtc aca tgc gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc 200 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 40 45 50 aag ttc aac tgg tac gtg gac ggc gtg gag gtg cat aat gcc aag aca 248 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 55 60 65 70 aag ccg cgg gag gag cag tac aac agc acg tac cgt gtg gtc agc gtc 296 Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 75 80 85 ctc acc gtc ctg cac cag gac tgg ctg aat ggc aag gag tac aag tgc 344 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 90 95 100 aag gtc tcc aac aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc 392 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 105 110 115 aaa gcc aaa ggg cag ccc cga gaa cca cag gtg tac acc ctg ccc cca 440 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 120 125 130 tcc cgg gat gag ctg acc aag aac cag gtc agc ctg acc tgc ctg gtc 488 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 135 140 145 150 aaa ggc ttc tat ccc agc gac atc gcc gtg gag tgg gag agc aat ggg 536 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 155 160 165 cag ccg gag aac aac tac aag acc acg cct ccc gtg ctg gac tcc gac 584 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 170 175 180 ggc tcc ttc ttc ctc tac agc aag ctc acc gtg gac aag agc agg tgg 632 Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 185 190 195 cag cag ggg aac gtc ttc tca tgc tcc gtg atg cat gag gct ctg cac 680 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 200 205 210 aac cac tac acg cag aag agc ctc tcc ctg tct ccg ggt aaa ggt gga 728 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly 215 220 225 230 ggt ggt ggt atc gaa ggt ccg act ctg cgt cag tgg ctg gct gct cgt 776 Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg 235 240 245 gct taatctcgag gatcc 794 Ala <210> SEQ ID NO 6 <211> LENGTH: 247 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <400> SEQUENCE: 6 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg 225 230 235 240 Gln Trp Leu Ala Ala Arg Ala 245 <210> SEQ ID NO 7 <211> LENGTH: 861 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP-TMP <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (39)..(842) <223> OTHER INFORMATION: <400> SEQUENCE: 7 tctagatttg ttttaactaa ttaaaggagg aataacat atg gac aaa act cac aca 56 Met Asp Lys Thr His Thr 1 5 tgt cca cct tgt cca gct ccg gaa ctc ctg ggg gga ccg tca gtc ttc 104 Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 10 15 20 ctc ttc ccc cca aaa ccc aag gac acc ctc atg atc tcc cgg acc cct 152 Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 25 30 35 gag gtc aca tgc gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc 200 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 40 45 50 aag ttc aac tgg tac gtg gac ggc gtg gag gtg cat aat gcc aag aca 248 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 55 60 65 70 aag ccg cgg gag gag cag tac aac agc acg tac cgt gtg gtc agc gtc 296 Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 75 80 85 ctc acc gtc ctg cac cag gac tgg ctg aat ggc aag gag tac aag tgc 344 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 90 95 100 aag gtc tcc aac aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc 392 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 105 110 115 aaa gcc aaa ggg cag ccc cga gaa cca cag gtg tac acc ctg ccc cca 440 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 120 125 130 tcc cgg gat gag ctg acc aag aac cag gtc agc ctg acc tgc ctg gtc 488 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 135 140 145 150 aaa ggc ttc tat ccc agc gac atc gcc gtg gag tgg gag agc aat ggg 536 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 155 160 165 cag ccg gag aac aac tac aag acc acg cct ccc gtg ctg gac tcc gac 584 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 170 175 180 ggc tcc ttc ttc ctc tac agc aag ctc acc gtg gac aag agc agg tgg 632 Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 185 190 195 cag cag ggg aac gtc ttc tca tgc tcc gtg atg cat gag gct ctg cac 680 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 200 205 210 aac cac tac acg cag aag agc ctc tcc ctg tct ccg ggt aaa ggt gga 728 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly 215 220 225 230 ggt ggt ggt atc gaa ggt ccg act ctg cgt cag tgg ctg gct gct cgt 776 Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg 235 240 245 gct ggt ggt gga ggt ggc ggc gga ggt att gag ggc cca acc ctt cgc 824 Ala Gly Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg 250 255 260 caa tgg ctt gca gca cgc gcataatctc gaggatccg 861 Gln Trp Leu Ala Ala Arg 265 <210> SEQ ID NO 8 <211> LENGTH: 268 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP-TMP <400> SEQUENCE: 8 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg 225 230 235 240 Gln Trp Leu Ala Ala Arg Ala Gly Gly Gly Gly Gly Gly Gly Gly Ile 245 250 255 Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg 260 265 <210> SEQ ID NO 9 <211> LENGTH: 855 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (39)..(845) <223> OTHER INFORMATION: <400> SEQUENCE: 9 tctagatttg ttttaactaa ttaaaggagg aataacat atg atc gaa ggt ccg act 56 Met Ile Glu Gly Pro Thr 1 5 ctg cgt cag tgg ctg gct gct cgt gct ggc ggt ggt ggc gga ggg ggt 104 Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly Gly Gly Gly Gly Gly 10 15 20 ggc att gag ggc cca acc ctt cgc caa tgg ctt gca gca cgc gca ggg 152 Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly 25 30 35 gga ggc ggt ggg gac aaa act cac aca tgt cca cct tgc cca gca cct 200 Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 40 45 50 gaa ctc ctg ggg gga ccg tca gtt ttc ctc ttc ccc cca aaa ccc aag 248 Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 55 60 65 70 gac acc ctc atg atc tcc cgg acc cct gag gtc aca tgc gtg gtg gtg 296 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 75 80 85 gac gtg agc cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac 344 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 90 95 100 ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg gag gag cag tac 392 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 105 110 115 aac agc acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac 440 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 120 125 130 tgg ctg aat ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc 488 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 135 140 145 150 cca gcc ccc atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga 536 Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 155 160 165 gaa cca cag gtg tac acc ctg ccc cca tcc cgg gat gag ctg acc aag 584 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 170 175 180 aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac 632 Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 185 190 195 atc gcc gtg gag tgg gag agc aat ggg cag ccg gag aac aac tac aag 680 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 200 205 210 acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc 728 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 215 220 225 230 aag ctc acc gtg gac aag agc agg tgg cag cag ggg aac gtc ttc tca 776 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 235 240 245 tgc tcc gtg atg cat gag gct ctg cac aac cac tac acg cag aag agc 824 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 250 255 260 ctc tcc ctg tct ccg ggt aaa taatggatcc 855 Leu Ser Leu Ser Pro Gly Lys 265 <210> SEQ ID NO 10 <211> LENGTH: 269 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 10 Met Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp 20 25 30 Leu Ala Ala Arg Ala Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys 35 40 45 Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 50 55 60 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 65 70 75 80 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 85 90 95 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 100 105 110 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 115 120 125 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 130 135 140 Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 145 150 155 160 Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 165 170 175 Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 180 185 190 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 195 200 205 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 210 215 220 Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 225 230 235 240 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 245 250 255 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 260 265 <210> SEQ ID NO 11 <211> LENGTH: 789 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (39)..(779) <223> OTHER INFORMATION: <400> SEQUENCE: 11 tctagatttg ttttaactaa ttaaaggagg aataacat atg atc gaa ggt ccg act 56 Met Ile Glu Gly Pro Thr 1 5 ctg cgt cag tgg ctg gct gct cgt gct ggt gga ggc ggt ggg gac aaa 104 Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly Gly Gly Gly Asp Lys 10 15 20 act cac aca tgt cca cct tgc cca gca cct gaa ctc ctg ggg gga ccg 152 Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 25 30 35 tca gtt ttc ctc ttc ccc cca aaa ccc aag gac acc ctc atg atc tcc 200 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 40 45 50 cgg acc cct gag gtc aca tgc gtg gtg gtg gac gtg agc cac gaa gac 248 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 55 60 65 70 cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg gag gtg cat aat 296 Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 75 80 85 gcc aag aca aag ccg cgg gag gag cag tac aac agc acg tac cgt gtg 344 Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 90 95 100 gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg aat ggc aag gag 392 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 105 110 115 tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc ccc atc gag aaa 440 Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 120 125 130 acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca cag gtg tac acc 488 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 135 140 145 150 ctg ccc cca tcc cgg gat gag ctg acc aag aac cag gtc agc ctg acc 536 Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 155 160 165 tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc gtg gag tgg gag 584 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 170 175 180 agc aat ggg cag ccg gag aac aac tac aag acc acg cct ccc gtg ctg 632 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 185 190 195 gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc acc gtg gac aag 680 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 200 205 210 agc agg tgg cag cag ggg aac gtc ttc tca tgc tcc gtg atg cat gag 728 Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 215 220 225 230 gct ctg cac aac cac tac acg cag aag agc ctc tcc ctg tct ccg ggt 776 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 235 240 245 aaa taatggatcc 789 Lys <210> SEQ ID NO 12 <211> LENGTH: 247 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-Fc <400> SEQUENCE: 12 Met Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly 1 5 10 15 Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 20 25 30 Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 35 40 45 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 50 55 60 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 65 70 75 80 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 85 90 95 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 100 105 110 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 115 120 125 Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 130 135 140 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 145 150 155 160 Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 165 170 175 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 180 185 190 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 195 200 205 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 210 215 220 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 225 230 235 240 Leu Ser Leu Ser Pro Gly Lys 245 <210> SEQ ID NO 13 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP <400> SEQUENCE: 13 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 1 5 10 <210> SEQ ID NO 14 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP <400> SEQUENCE: 14 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 15 <211> LENGTH: 812 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (39)..(797) <223> OTHER INFORMATION: <400> SEQUENCE: 15 tctagatttg ttttaactaa ttaaaggagg aataacat atg gac aaa act cac aca 56 Met Asp Lys Thr His Thr 1 5 tgt cca cct tgt cca gct ccg gaa ctc ctg ggg gga ccg tca gtc ttc 104 Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 10 15 20 ctc ttc ccc cca aaa ccc aag gac acc ctc atg atc tcc cgg acc cct 152 Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 25 30 35 gag gtc aca tgc gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc 200 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 40 45 50 aag ttc aac tgg tac gtg gac ggc gtg gag gtg cat aat gcc aag aca 248 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 55 60 65 70 aag ccg cgg gag gag cag tac aac agc acg tac cgt gtg gtc agc gtc 296 Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 75 80 85 ctc acc gtc ctg cac cag gac tgg ctg aat ggc aag gag tac aag tgc 344 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 90 95 100 aag gtc tcc aac aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc 392 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 105 110 115 aaa gcc aaa ggg cag ccc cga gaa cca cag gtg tac acc ctg ccc cca 440 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 120 125 130 tcc cgg gat gag ctg acc aag aac cag gtc agc ctg acc tgc ctg gtc 488 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 135 140 145 150 aaa ggc ttc tat ccc agc gac atc gcc gtg gag tgg gag agc aat ggg 536 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 155 160 165 cag ccg gag aac aac tac aag acc acg cct ccc gtg ctg gac tcc gac 584 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 170 175 180 ggc tcc ttc ttc ctc tac agc aag ctc acc gtg gac aag agc agg tgg 632 Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 185 190 195 cag cag ggg aac gtc ttc tca tgc tcc gtg atg cat gag gct ctg cac 680 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 200 205 210 aac cac tac acg cag aag agc ctc tcc ctg tct ccg ggt aaa ggt gga 728 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly 215 220 225 230 ggt ggt ggt gga ggt act tac tct tgc cac ttc ggc ccg ctg act tgg 776 Gly Gly Gly Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp 235 240 245 gtt tgc aaa ccg cag ggt ggt taatctcgtg gatcc 812 Val Cys Lys Pro Gln Gly Gly 250 <210> SEQ ID NO 16 <211> LENGTH: 253 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 16 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His 225 230 235 240 Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly 245 250 <210> SEQ ID NO 17 <211> LENGTH: 807 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (39)..(797) <223> OTHER INFORMATION: <400> SEQUENCE: 17 tctagatttg ttttaactaa ttaaaggagg aataacat atg gga ggt act tac tct 56 Met Gly Gly Thr Tyr Ser 1 5 tgc cac ttc ggc ccg ctg act tgg gta tgt aag cca caa ggg ggt ggg 104 Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly 10 15 20 gga ggc ggg ggg gac aaa act cac aca tgt cca cct tgc cca gca cct 152 Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 25 30 35 gaa ctc ctg ggg gga ccg tca gtt ttc ctc ttc ccc cca aaa ccc aag 200 Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 40 45 50 gac acc ctc atg atc tcc cgg acc cct gag gtc aca tgc gtg gtg gtg 248 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 55 60 65 70 gac gtg agc cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac 296 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 75 80 85 ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg gag gag cag tac 344 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 90 95 100 aac agc acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac 392 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 105 110 115 tgg ctg aat ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc 440 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 120 125 130 cca gcc ccc atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga 488 Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 135 140 145 150 gaa cca cag gtg tac acc ctg ccc cca tcc cgg gat gag ctg acc aag 536 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 155 160 165 aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac 584 Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 170 175 180 atc gcc gtg gag tgg gag agc aat ggg cag ccg gag aac aac tac aag 632 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 185 190 195 acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc 680 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 200 205 210 aag ctc acc gtg gac aag agc agg tgg cag cag ggg aac gtc ttc tca 728 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 215 220 225 230 tgc tcc gtg atg cat gag gct ctg cac aac cac tac acg cag aag agc 776 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 235 240 245 ctc tcc ctg tct ccg ggt aaa taatggatcc 807 Leu Ser Leu Ser Pro Gly Lys 250 <210> SEQ ID NO 18 <211> LENGTH: 253 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <400> SEQUENCE: 18 Met Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys 1 5 10 15 Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys 20 25 30 Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 35 40 45 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 50 55 60 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 65 70 75 80 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 85 90 95 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 100 105 110 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 115 120 125 Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 130 135 140 Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 145 150 155 160 Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 165 170 175 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 180 185 190 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 195 200 205 Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 210 215 220 Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 225 230 235 240 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 245 250 <210> SEQ ID NO 19 <211> LENGTH: 881 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (41)..(871) <223> OTHER INFORMATION: <400> SEQUENCE: 19 tctagatttg agttttaact tttagaagga ggaataaaat atg gga ggt act tac 55 Met Gly Gly Thr Tyr 1 5 tct tgc cac ttc ggc cca ctg act tgg gtt tgc aaa ccg cag ggt ggc 103 Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly 10 15 20 ggc ggc ggc ggc ggt ggt acc tat tcc tgt cat ttt ggc ccg ctg acc 151 Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr 25 30 35 tgg gta tgt aag cca caa ggg ggt ggg gga ggc ggg ggg gac aaa act 199 Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Asp Lys Thr 40 45 50 cac aca tgt cca cct tgc cca gca cct gaa ctc ctg ggg gga ccg tca 247 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 55 60 65 gtt ttc ctc ttc ccc cca aaa ccc aag gac acc ctc atg atc tcc cgg 295 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 70 75 80 85 acc cct gag gtc aca tgc gtg gtg gtg gac gtg agc cac gaa gac cct 343 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 90 95 100 gag gtc aag ttc aac tgg tac gtg gac ggc gtg gag gtg cat aat gcc 391 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 105 110 115 aag aca aag ccg cgg gag gag cag tac aac agc acg tac cgt gtg gtc 439 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 120 125 130 agc gtc ctc acc gtc ctg cac cag gac tgg ctg aat ggc aag gag tac 487 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 135 140 145 aag tgc aag gtc tcc aac aaa gcc ctc cca gcc ccc atc gag aaa acc 535 Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 150 155 160 165 atc tcc aaa gcc aaa ggg cag ccc cga gaa cca cag gtg tac acc ctg 583 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 170 175 180 ccc cca tcc cgg gat gag ctg acc aag aac cag gtc agc ctg acc tgc 631 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 185 190 195 ctg gtc aaa ggc ttc tat ccc agc gac atc gcc gtg gag tgg gag agc 679 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 200 205 210 aat ggg cag ccg gag aac aac tac aag acc acg cct ccc gtg ctg gac 727 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 215 220 225 tcc gac ggc tcc ttc ttc ctc tac agc aag ctc acc gtg gac aag agc 775 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 230 235 240 245 agg tgg cag cag ggg aac gtc ttc tca tgc tcc gtg atg cat gag gct 823 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 250 255 260 ctg cac aac cac tac acg cag aag agc ctc tcc ctg tct ccg ggt aaa 871 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 265 270 275 taatggatcc 881<210> SEQ ID NO 20<211> LENGTH: 277 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 20 Met Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys 1 5 10 15 Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His 20 25 30 Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly 35 40 45 Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 50 55 60 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 65 70 75 80 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 85 90 95 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 100 105 110 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 115 120 125 Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 130 135 140 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 145 150 155 160 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 165 170 175 Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 180 185 190 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 195 200 205 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 210 215 220 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 225 230 235 240 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 245 250 255 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 260 265 270 Leu Ser Pro Gly Lys 275 <210> SEQ ID NO 21<211> LENGTH: 885 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP-EMP <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (39)..(869) <223> OTHER INFORMATION: <400> SEQUENCE: 21 tctagatttg ttttaactaa ttaaaggagg aataacat atg gac aaa act cac aca 56 Met Asp Lys Thr His Thr 1 5 tgt cca cct tgc cca gca cct gaa ctc ctg ggg gga ccg tca gtt ttc 104 Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 10 15 20 ctc ttc ccc cca aaa ccc aag gac acc ctc atg atc tcc cgg acc cct 152 Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 25 30 35 gag gtc aca tgc gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc 200 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 40 45 50 aag ttc aac tgg tac gtg gac ggc gtg gag gtg cat aat gcc aag aca 248 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 55 60 65 70 aag ccg cgg gag gag cag tac aac agc acg tac cgt gtg gtc agc gtc 296 Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 75 80 85 ctc acc gtc ctg cac cag gac tgg ctg aat ggc aag gag tac aag tgc 344 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 90 95 100 aag gtc tcc aac aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc 392 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 105 110 115 aaa gcc aaa ggg cag ccc cga gaa cca cag gtg tac acc ctg cct cca 440 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 120 125 130 tcc cgg gat gag ctg acc aag aac cag gtc agc ctg acc tgc ctg gtc 488 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 135 140 145 150 aaa ggc ttc tat ccc agc gac atc gcc gtg gag tgg gag agc aat ggg 536 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 155 160 165 cag ccg gag aac aac tac aag acc acg cct ccc gtg ctg gac tcc gac 584 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 170 175 180 ggc tcc ttc ttc ctc tac agc aag ctc acc gtg gac aag agc agg tgg 632 Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 185 190 195 cag cag ggg aac gtc ttc tca tgc tcc gtg atg cat gag gct ctg cac 680 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 200 205 210 aac cac tac acg cag aag agc ctc tcc ctg tct ccg ggt aaa ggt gga 728 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly 215 220 225 230 ggt ggt ggc gga ggt act tac tct tgc cac ttc ggc cca ctg act tgg 776 Gly Gly Gly Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp 235 240 245 gtt tgc aaa ccg cag ggt ggc ggc ggc ggc ggc ggt ggt acc tat tcc 824 Val Cys Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser 250 255 260 tgt cat ttt ggc ccg ctg acc tgg gta tgt aag cca caa ggg ggt 869 Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly 265 270 275 taatctcgag gatcca 885 <210> SEQ ID NO 22<211> LENGTH: 277 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP-EMP <400> SEQUENCE: 22 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His 225 230 235 240 Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly 245 250 255 Gly Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys 260 265 270 Lys Pro Gln Gly Gly 275 <210> SEQ ID NO 23 <211> LENGTH: 1546 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: pAMG21 <400> SEQUENCE: 23 gcgtaacgta tgcatggtct ccccatgcga gagtagggaa ctgccaggca tcaaataaaa 60 cgaaaggctc agtcgaaaga ctgggccttt cgttttatct gttgtttgtc ggtgaacgct 120ctcctgagta ggacaaatcc gccgggagcg gatttgaacg ttgcgaagca acggcccgga 180 gggtggcggg caggacgccc gccataaact gccaggcatc aaattaagca gaaggccatc 240 ctgacggatg gcctttttgc gtttctacaa actcttttgt ttatttttct aaatacattc 300aaatatggac gtcgtactta acttttaaag tatgggcaat caattgctcc tgttaaaatt 360 gctttagaaa tactttggca gcggtttgtt gtattgagtt tcatttgcgc attggttaaa 420 tggaaagtga ccgtgcgctt actacagcct aatatttttg aaatatccca agagcttttt 480 ccttcgcatg cccacgctaa acattctttt tctcttttgg ttaaatcgtt gtttgattta 540 ttatttgcta tatttatttt tcgataatta tcaactagag aaggaacaat taatggtatg 600 ttcatacacg catgtaaaaa taaactatct atatagttgt ctttctctga atgtgcaaaa 660ctaagcattc cgaagccatt attagcagta tgaataggga aactaaaccc agtgataaga 720 cctgatgatt tcgcttcttt aattacattt ggagattttt tatttacagc attgttttca 780 aatatattcc aattaatcgg tgaatgattg gagttagaat aatctactat aggatcatat 840 tttattaaat tagcgtcatc ataatattgc ctccattttt tagggtaatt atccagaatt 900 gaaatatcag atttaaccat agaatgagga taaatgatcg cgagtaaata atattcacaa 960 tgtaccattt tagtcatatc agataagcat tgattaatat cattattgct tctacaggct 1020 ttaattttat taattattct gtaagtgtcg tcggcattta tgtctttcat acccatctct 1080 ttatccttac ctattgtttg tcgcaagttt tgcgtgttat atatcattaa aacggtaata 1140 gattgacatt tgattctaat aaattggatt tttgtcacac tattatatcg cttgaaatac 1200 aattgtttaa cataagtacc tgtaggatcg tacaggttta cgcaagaaaa tggtttgtta 1260 tagtcgatta atcgatttga ttctagattt gttttaacta attaaaggag gaataacata 1320 tggttaacgc gttggaattc gagctcacta gtgtcgacct gcagggtacc atggaagctt 1380 actcgaggat ccgcggaaag aagaagaaga agaagaaagc ccgaaaggaa gctgagttgg 1440 ctgctgccac cgctgagcaa taactagcat aaccccttgg ggcctctaaa cgggtcttga 1500ggggtttttt gctgaaagga ggaaccgctc ttcacgctct tcacgc 1546 <210> SEQ ID NO 24 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 24 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Lys Ala 1 5 10 <210> SEQ ID NO 25 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 25 Ile Glu Gly Pro Thr Leu Arg Glu Trp Leu Ala Ala Arg Ala 1 5 10 <210> SEQ ID NO 26 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: At position 14, amino acid linker to anidentical sequence <400> SEQUENCE: 26 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 1 5 10 <210> SEQ ID NO 27 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: At position 14, amino acid linker to anidentical sequence <400> SEQUENCE: 27 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Lys Ala 1 5 10 <210> SEQ ID NO 28<211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: At position 9 disulfide linkage to position 9of an identical sequence <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: At position 14, amino acid linker to anidentical sequence <400> SEQUENCE: 28 Ile Glu Gly Pro Thr Leu Arg Gln Cys Leu Ala Ala Arg Ala 1 5 10 <210> SEQ ID NO 29 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16)..(16) <223> OTHER INFORMATION: Position 16 bromoacetyl group linked tosidechain <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: At position 14, amino acid linker attachedN-to-C to Lys and to another linker and an identical sequence <400> SEQUENCE: 29 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 1 5 10 <210> SEQ ID NO 30<211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16)..(16) <223> OTHER INFORMATION: Position 16 polyethylene glycol linked tosidechain <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: At position 14, amino acid linker attachedN-to-C to Lys and to another linker and an identical sequence <400> SEQUENCE: 30 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 1 5 10 <210> SEQ ID NO 31 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Position 9 disulfide bond to residue 9 of aseparate identical sequence <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: At position 14, amino acid linker to anidentical sequence <400> SEQUENCE: 31 Ile Glu Gly Pro Thr Leu Arg Gln Cys Leu Ala Ala Arg Ala 1 5 10 <210> SEQ ID NO 32 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: At position 14, amino acid linker attachmentsite <400> SEQUENCE: 32 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 1 5 10 <210> SEQ ID NO 33 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6, 7 and)..(8) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 33 Val Arg Asp Gln Ile Xaa Xaa Xaa Leu 1 5 <210> SEQ ID NO 34 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 34 Thr Leu Arg Glu Trp Leu 1 5 <210> SEQ ID NO 35<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 35 Gly Arg Val Arg Asp Gln Val Ala Gly Trp 1 5 10 <210> SEQ ID NO 36 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 36 Gly Arg Val Lys Asp Gln Ile Ala Gln Leu 1 5 10 <210> SEQ ID NO 37 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 37 Gly Val Arg Asp Gln Val Ser Trp Ala Leu 1 5 10 <210> SEQ ID NO 38 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 38 Glu Ser Val Arg Glu Gln Val Met Lys Tyr 1 5 10 <210> SEQ ID NO 39 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 39 Ser Val Arg Ser Gln Ile Ser Ala Ser Leu 1 5 10 <210> SEQ ID NO 40<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 40 Gly Val Arg Glu Thr Val Tyr Arg His Met 1 5 10 <210> SEQ ID NO 41 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 41 Gly Val Arg Glu Val Ile Val Met His Met Leu 1 5 10 <210> SEQ ID NO 42<211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 42 Gly Arg Val Arg Asp Gln Ile Trp Ala Ala Leu 1 5 10 <210> SEQ ID NO 43 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 43 Ala Gly Val Arg Asp Gln Ile Leu Ile Trp Leu 1 5 10 <210> SEQ ID NO 44 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 44 Gly Arg Val Arg Asp Gln Ile Met Leu Ser Leu 1 5 10 <210> SEQ ID NO 45<211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(10) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 45 Gly Arg Val Arg Asp Gln Ile Xaa Xaa Xaa Leu 1 5 10 <210> SEQ ID NO 46 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 46 Cys Thr Leu Arg Gln Trp Leu Gln Gly Cys 1 5 10 <210> SEQ ID NO 47 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 47 Cys Thr Leu Gln Glu Phe Leu Glu Gly Cys 1 5 10 <210> SEQ ID NO 48 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 48 Cys Thr Arg Thr Glu Trp Leu His Gly Cys 1 5 10 <210> SEQ ID NO 49<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 49 Cys Thr Leu Arg Glu Trp Leu His Gly Gly Phe Cys 1 5 10 <210> SEQ ID NO 50<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 50 Cys Thr Leu Arg Glu Trp Val Phe Ala Gly Leu Cys 1 5 10 <210> SEQ ID NO 51 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 51 Cys Thr Leu Arg Gln Trp Leu Ile Leu Leu Gly Met Cys 1 5 10 <210> SEQ ID NO 52 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 52 Cys Thr Leu Ala Glu Phe Leu Ala Ser Gly Val Glu Gln Cys 1 5 10 <210> SEQ ID NO 53 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 53 Cys Ser Leu Gln Glu Phe Leu Ser His Gly Gly Tyr Val Cys 1 5 10 <210> SEQ ID NO 54 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 54 Cys Thr Leu Arg Glu Phe Leu Asp Pro Thr Thr Ala Val Cys 1 5 10 <210> SEQ ID NO 55<211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 55 Cys Thr Leu Lys Glu Trp Leu Val Ser His Glu Val Trp Cys 1 5 10 <210> SEQ ID NO 56 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(9) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 56 Cys Thr Leu Arg Glu Trp Leu Xaa Xaa Cys 1 5 10 <210> SEQ ID NO 57 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(10) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 57 Cys Thr Leu Arg Glu Trp Leu Xaa Xaa Xaa Cys 1 5 10 <210> SEQ ID NO 58 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(11) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 58 Cys Thr Leu Arg Glu Trp Leu Xaa Xaa Xaa Xaa Cys 1 5 10 <210> SEQ ID NO 59 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(12) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 59 Cys Thr Leu Arg Glu Trp Leu Xaa Xaa Xaa Xaa Xaa Cys 1 5 10 <210> SEQ ID NO 60<211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(13) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 60 Cys Thr Leu Arg Glu Trp Leu Xaa Xaa Xaa Xaa Xaa Xaa Cys 1 5 10 <210> SEQ ID NO 61<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 61 Arg Glu Gly Pro Thr Leu Arg Gln Trp Met 1 5 10 <210> SEQ ID NO 62 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 62 Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala 1 5 10 <210> SEQ ID NO 63 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 63 Glu Arg Gly Pro Phe Trp Ala Lys Ala Cys 1 5 10 <210> SEQ ID NO 64 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 64 Arg Glu Gly Pro Arg Cys Val Met Trp Met 1 5 10 <210> SEQ ID NO 65<211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 65 Cys Gly Thr Glu Gly Pro Thr Leu Ser Thr Trp Leu Asp Cys 1 5 10 <210> SEQ ID NO 66 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 66 Cys Glu Gln Asp Gly Pro Thr Leu Leu Glu Trp Leu Lys Cys 1 5 10 <210> SEQ ID NO 67 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 67 Cys Glu Leu Val Gly Pro Ser Leu Met Ser Trp Leu Thr Cys 1 5 10 <210> SEQ ID NO 68 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 68 Cys Leu Thr Gly Pro Phe Val Thr Gln Trp Leu Tyr Glu Cys 1 5 10 <210> SEQ ID NO 69 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 69 Cys Arg Ala Gly Pro Thr Leu Leu Glu Trp Leu Thr Leu Cys 1 5 10 <210> SEQ ID NO 70<211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 70 Cys Ala Asp Gly Pro Thr Leu Arg Glu Trp Ile Ser Phe Cys 1 5 10 <210> SEQ ID NO 71 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2 )..(12) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 71 Cys Xaa Glu Gly Pro Thr Leu Arg Glu Trp Leu Xaa Cys 1 5 10 <210> SEQ ID NO 72 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3 )..(13) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 72 Cys Xaa Xaa Glu Gly Pro Thr Leu Arg Glu Trp Leu Xaa Cys 1 5 10 <210> SEQ ID NO 73 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 12 )..(13) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 73 Cys Xaa Glu Gly Pro Thr Leu Arg Glu Trp Leu Xaa Xaa Cys 1 5 10 <210> SEQ ID NO 74 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3, 13 )..(14) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 74 Cys Xaa Xaa Glu Gly Pro Thr Leu Arg Glu Trp Leu Xaa Xaa Cys 1 5 10 15 <210> SEQ ID NO 75<211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 75 Gly Gly Cys Thr Leu Arg Glu Trp Leu His Gly Gly Phe Cys Gly Gly 1 5 10 15 <210> SEQ ID NO 76 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 76 Gly Gly Cys Ala Asp Gly Pro Thr Leu Arg Glu Trp Ile Ser Phe Cys 1 5 10 15 Gly Gly <210> SEQ ID NO 77 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 77 Gly Asn Ala Asp Gly Pro Thr Leu Arg Gln Trp Leu Glu Gly Arg Arg 1 5 10 15 Pro Lys Asn <210> SEQ ID NO 78 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 78 Leu Ala Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu His Gly Asn Gly 1 5 10 15 Arg Asp Thr <210> SEQ ID NO 79 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 79 His Gly Arg Val Gly Pro Thr Leu Arg Glu Trp Lys Thr Gln Val Ala 1 5 10 15 Thr Lys Lys <210> SEQ ID NO 80 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 80 Thr Ile Lys Gly Pro Thr Leu Arg Gln Trp Leu Lys Ser Arg Glu His 1 5 10 15 Thr Ser <210> SEQ ID NO 81<211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDE <400> SEQUENCE: 81 Ile Ser Asp Gly Pro Thr Leu Lys Glu Trp Leu Ser Val Thr Arg Gly 1 5 10 15 Ala Ser <210> SEQ ID NO 82 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO MIMETIC PEPTIDE <400> SEQUENCE: 82 Ser Ile Glu Gly Pro Thr Leu Arg Glu Trp Leu Thr Ser Arg Thr Pro 1 5 10 15 His Ser <210> SEQ ID NO 83 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 4, 5, 8, 11 )..(13) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 83 Tyr Xaa Cys Xaa Xaa Gly Pro Xaa Thr Trp Xaa Cys Xaa Pro 1 5 10 <210> SEQ ID NO 84 <211> LENGTH: 28 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 4, 5, 8, 11, 13, 16, 18, 19, 22, 25 )..(27) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 84 Tyr Xaa Cys Xaa Xaa Gly Pro Xaa Thr Trp Xaa Cys Xaa Pro Tyr Xaa 1 5 10 15 Cys Xaa Xaa Gly Pro Xaa Thr Trp Xaa Cys Xaa Pro 20 25 <210> SEQ ID NO 85 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: At position 14, amino acid linker to anidentical sequence <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 4, 5, 8, 11)..(13) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 85 Tyr Xaa Cys Xaa Xaa Gly Pro Xaa Thr Trp Xaa Cys Xaa Pro 1 5 10 <210> SEQ ID NO 86 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 4, 5, 8, 11 )..(13) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 86 Tyr Xaa Cys Xaa Xaa Gly Pro Xaa Thr Trp Xaa Cys Xaa Pro 1 5 10 <210> SEQ ID NO 87 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 87 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly 20 <210> SEQ ID NO 88 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 88 Gly Gly Asp Tyr His Cys Arg Met Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Leu Gly Gly 20 <210> SEQ ID NO 89 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 89 Gly Gly Val Tyr Ala Cys Arg Met Gly Pro Ile Thr Trp Val Cys Ser 1 5 10 15 Pro Leu Gly Gly 20 <210> SEQ ID NO 90 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 90 Val Gly Asn Tyr Met Cys His Phe Gly Pro Ile Thr Trp Val Cys Arg 1 5 10 15 Pro Gly Gly Gly 20 <210> SEQ ID NO 91 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 91 Gly Gly Leu Tyr Leu Cys Arg Phe Gly Pro Val Thr Trp Asp Cys Gly 1 5 10 15 Tyr Lys Gly Gly 20 <210> SEQ ID NO 92 <211> LENGTH: 40 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 92 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr 20 25 30 Trp Val Cys Lys Pro Gln Gly Gly 35 40 <210> SEQ ID NO 93 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (20)..(20) <223> OTHER INFORMATION: Position 20, amino acid linker to an identicalsequence <400> SEQUENCE: 93 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly 20 <210> SEQ ID NO 94 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 94 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly Ser Ser Lys 20 <210> SEQ ID NO 95 <211> LENGTH: 46 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 95 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly Ser Ser Lys Gly Gly Thr Tyr Ser Cys His Phe Gly 20 25 30 Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Ser Ser Lys 35 40 45 <210> SEQ ID NO 96 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (23)..(23) <223> OTHER INFORMATION: Position 23, amino acid linker to an identical sequence <400> SEQUENCE: 96 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly Ser Ser Lys 20 <210> SEQ ID NO 97 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (22)..(22) <223> OTHER INFORMATION: Position 22 linked through epsilon amine tolysyl, which is linked to a separate identical sequence through that sequence′s alpha amine <400> SEQUENCE: 97 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly Ser Ser 20 <210> SEQ ID NO 98 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (23)..(23) <223> OTHER INFORMATION: At position 23 biotin linked to the sidechain through a linker <400> SEQUENCE: 98 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly Ser Ser Lys 20 <210> SEQ ID NO 99 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: G-CSF-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: At position 4 disulfide bond to residue 4 of aseparate identical sequence <400> SEQUENCE: 99 Glu Glu Asp Cys Lys 1 5 <210> SEQ ID NO 100 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: G-CSF-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: At position 4, Xaa is an isoteric ethylenespacer linked to a separate identical sequence <400> SEQUENCE: 100 Glu Glu Asp Xaa Lys 1 5 <210> SEQ ID NO 101 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: G-CSF-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a pyroglutamic acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is an isoteric ethylene spacerlinked to a separate identical sequence. <400> SEQUENCE: 101 Xaa Gly Glu Asp Xaa Lys 1 5 <210> SEQ ID NO 102 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: G-CSF-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a picolinic acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is an isoteric ethylene spacerlinked to a separate identical sequence. <400> SEQUENCE: 102 Xaa Ser Asp Xaa Lys 1 5 <210> SEQ ID NO 103 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: G-CSF-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: At position 5, amino acid linker to anidentical sequence <400> SEQUENCE: 103 Glu Glu Asp Cys Lys 1 5 <210> SEQ ID NO 104 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: G-CSF-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: At position 5, amino acid linker to anidentical sequence <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 104 Glu Glu Asp Xaa Lys 1 5 <210> SEQ ID NO 105 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIVIRAL (HBV) <400> SEQUENCE: 105 Leu Leu Gly Arg Met Lys 1 5 <210> SEQ ID NO 106<211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 106 Tyr Cys Phe Thr Ala Ser Glu Asn His Cys Tyr 1 5 10 <210> SEQ ID NO 107 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 107 Tyr Cys Phe Thr Asn Ser Glu Asn His Cys Tyr 1 5 10 <210> SEQ ID NO 108 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 108 Tyr Cys Phe Thr Arg Ser Glu Asn His Cys Tyr 1 5 10 <210> SEQ ID NO 109 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 109 Phe Cys Ala Ser Glu Asn His Cys Tyr 1 5 <210> SEQ ID NO 110 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 110 Tyr Cys Ala Ser Glu Asn His Cys Tyr 1 5 <210> SEQ ID NO 111 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 111 Phe Cys Asn Ser Glu Asn His Cys Tyr 1 5 <210> SEQ ID NO 112 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 112 Phe Cys Asn Ser Glu Asn Arg Cys Tyr 1 5 <210> SEQ ID NO 113 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 113 Phe Cys Asn Ser Val Glu Asn Arg Cys Tyr 1 5 10 <210> SEQ ID NO 114 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 114 Tyr Cys Ser Gln Ser Val Ser Asn Asp Cys Phe 1 5 10 <210> SEQ ID NO 115 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 115 Phe Cys Val Ser Asn Asp Arg Cys Tyr 1 5 <210> SEQ ID NO 116 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 116 Tyr Cys Arg Lys Glu Leu Gly Gln Val Cys Tyr 1 5 10 <210> SEQ ID NO 117 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 117 Tyr Cys Lys Glu Pro Gly Gln Cys Tyr 1 5 <210> SEQ ID NO 118 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 118 Tyr Cys Arg Lys Glu Met Gly Cys Tyr 1 5 <210> SEQ ID NO 119 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 119 Phe Cys Arg Lys Glu Met Gly Cys Tyr 1 5 <210> SEQ ID NO 120<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 120 Tyr Cys Trp Ser Gln Asn Leu Cys Tyr 1 5 <210> SEQ ID NO 121<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 121 Tyr Cys Glu Leu Ser Gln Tyr Leu Cys Tyr 1 5 10 <210> SEQ ID NO 122 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 122 Tyr Cys Trp Ser Gln Asn Tyr Cys Tyr 1 5 <210> SEQ ID NO 123 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF ANTAGONIST PEPTIDE <400> SEQUENCE: 123 Tyr Cys Trp Ser Gln Tyr Leu Cys Tyr 1 5 <210> SEQ ID NO 124 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Xaa (Pos1) can be C, A, a-amino-g-bromobutyric acid or Hoc. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Xaa can be R, H, L or W. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Xaa can be M, F or I. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Xaa can be any one of the 20 L-amino acids or the stereoisomeric D-amino acids. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Xaa can be D, E, I, L or V. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Xaa can be a-amino-g-bromobutyric acid or Hoc, provided that either Xaa (Pos1) or Xaa (Pos10) is C or Hoc. <400> SEQUENCE: 124 Xaa Xaa Xaa Gly Pro Xaa Thr Trp Xaa Xaa 1 5 10 <210> SEQ ID NO 125 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CTLA4-MIMETIC <400> SEQUENCE: 125 Gly Phe Val Cys Ser Gly Ile Phe Ala Val Gly Val Gly Arg Cys 1 5 10 15 <210> SEQ ID NO 126 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CTLA4-MIMETIC <400> SEQUENCE: 126 Ala Pro Gly Val Arg Leu Gly Cys Ala Val Leu Gly Arg Tyr Cys 1 5 10 15 <210> SEQ ID NO 127 <211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: C3B ANTAGONIST <400> SEQUENCE: 127 Ile Cys Val Val Gln Asp Trp Gly His His Arg Cys Thr Ala Gly His 1 5 10 15 Met Ala Asn Leu Thr Ser His Ala Ser Ala Ile 20 25 <210> SEQ ID NO 128 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: C3B ANTAGONIST <400> SEQUENCE: 128 Ile Cys Val Val Gln Asp Trp Gly His His Arg Cys Thr 1 5 10 <210> SEQ ID NO 129 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: C3B ANTAGONIST <400> SEQUENCE: 129 Cys Val Val Gln Asp Trp Gly His His Ala Cys 1 5 10 <210> SEQ ID NO 130 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 130 Thr Phe Ser Asp Leu Trp 1 5 <210> SEQ ID NO 131 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 131 Gln Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro 1 5 10 <210> SEQ ID NO 132 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 132 Gln Pro Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro 1 5 10 <210> SEQ ID NO 133 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 133 Gln Glu Thr Phe Ser Asp Tyr Trp Lys Leu Leu Pro 1 5 10 <210> SEQ ID NO 134 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 134 Gln Pro Thr Phe Ser Asp Tyr Trp Lys Leu Leu Pro 1 5 10 <210> SEQ ID NO 135 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 135 Met Pro Arg Phe Met Asp Tyr Trp Glu Gly Leu Asn 1 5 10 <210> SEQ ID NO 136 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 136 Val Gln Asn Phe Ile Asp Tyr Trp Thr Gln Gln Phe 1 5 10 <210> SEQ ID NO 137 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 137 Thr Gly Pro Ala Phe Thr His Tyr Trp Ala Thr Phe 1 5 10 <210> SEQ ID NO 138 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 138 Ile Asp Arg Ala Pro Thr Phe Arg Asp His Trp Phe Ala Leu Val 1 5 10 15 <210> SEQ ID NO 139 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 139 Pro Arg Pro Ala Leu Val Phe Ala Asp Tyr Trp Glu Thr Leu Tyr 1 5 10 15 <210> SEQ ID NO 140 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 140 Pro Ala Phe Ser Arg Phe Trp Ser Asp Leu Ser Ala Gly Ala His 1 5 10 15 <210> SEQ ID NO 141 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 141 Pro Ala Phe Ser Arg Phe Trp Ser Lys Leu Ser Ala Gly Ala His 1 5 10 15 <210> SEQ ID NO 142 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 4, 8 )..(9) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 142 Pro Xaa Phe Xaa Asp Tyr Trp Xaa Xaa Leu 1 5 10 <210> SEQ ID NO 143 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 143 Gln Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro 1 5 10 <210> SEQ ID NO 144 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 144 Gln Pro Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro 1 5 10 <210> SEQ ID NO 145 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 145 Gln Glu Thr Phe Ser Asp Tyr Trp Lys Leu Leu Pro 1 5 10 <210> SEQ ID NO 146 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MDM/HDM ANTAGONIST PEPTIDE <400> SEQUENCE: 146 Gln Pro Thr Phe Ser Asp Tyr Trp Lys Leu Leu Pro 1 5 10 <210> SEQ ID NO 147 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 147 Asp Ile Thr Trp Asp Gln Leu Trp Asp Leu Met Lys 1 5 10 <210> SEQ ID NO 148 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 148 Asp Ile Thr Trp Asp Glu Leu Trp Lys Ile Met Asn 1 5 10 <210> SEQ ID NO 149 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 149 Asp Tyr Thr Trp Phe Glu Leu Trp Asp Met Met Gln 1 5 10 <210> SEQ ID NO 150 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 150 Gln Ile Thr Trp Ala Gln Leu Trp Asn Met Met Lys 1 5 10 <210> SEQ ID NO 151 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 151 Asp Met Thr Trp His Asp Leu Trp Thr Leu Met Ser 1 5 10 <210> SEQ ID NO 152 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 152 Asp Tyr Ser Trp His Asp Leu Trp Glu Met Met Ser 1 5 10 <210> SEQ ID NO 153 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 153 Glu Ile Thr Trp Asp Gln Leu Trp Glu Val Met Asn 1 5 10 <210> SEQ ID NO 154 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 154 His Val Ser Trp Glu Gln Leu Trp Asp Ile Met Asn 1 5 10 <210> SEQ ID NO 155 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 155 His Ile Thr Trp Asp Gln Leu Trp Arg Ile Met Thr 1 5 10 <210> SEQ ID NO 156 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 156 Arg Asn Met Ser Trp Leu Glu Leu Trp Glu His Met Lys 1 5 10 <210> SEQ ID NO 157 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 157 Ala Glu Trp Thr Trp Asp Gln Leu Trp His Val Met Asn Pro Ala Glu 1 5 10 15 Ser Gln <210> SEQ ID NO 158 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 158 His Arg Ala Glu Trp Leu Ala Leu Trp Glu Gln Met Ser Pro 1 5 10 <210> SEQ ID NO 159 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 159 Lys Lys Glu Asp Trp Leu Ala Leu Trp Arg Ile Met Ser Val 1 5 10 <210> SEQ ID NO 160 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 160 Ile Thr Trp Asp Gln Leu Trp Asp Leu Met Lys 1 5 10 <210> SEQ ID NO 161 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 161 Asp Ile Thr Trp Asp Gln Leu Trp Asp Leu Met Lys 1 5 10 <210> SEQ ID NO 162 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 162 Asp Ile Thr Trp Asp Gln Leu Trp Asp Leu Met Lys 1 5 10 <210> SEQ ID NO 163 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 163 Asp Ile Thr Trp Asp Gln Leu Trp Asp Leu Met Lys 1 5 10 <210> SEQ ID NO 164 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 164 Ser Cys Val Lys Trp Gly Lys Lys Glu Phe Cys Gly Ser 1 5 10 <210> SEQ ID NO 165 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 165 Ser Cys Trp Lys Tyr Trp Gly Lys Glu Cys Gly Ser 1 5 10 <210> SEQ ID NO 166 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 166 Ser Cys Tyr Glu Trp Gly Lys Leu Arg Trp Cys Gly Ser 1 5 10 <210> SEQ ID NO 167 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 167 Ser Cys Leu Arg Trp Gly Lys Trp Ser Asn Cys Gly Ser 1 5 10 <210> SEQ ID NO 168 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 168 Ser Cys Trp Arg Trp Gly Lys Tyr Gln Ile Cys Gly Ser 1 5 10 <210> SEQ ID NO 169 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 169 Ser Cys Val Ser Trp Gly Ala Leu Lys Leu Cys Gly Ser 1 5 10 <210> SEQ ID NO 170 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 170 Ser Cys Ile Arg Trp Gly Gln Asn Thr Phe Cys Gly Ser 1 5 10 <210> SEQ ID NO 171 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 171 Ser Cys Trp Gln Trp Gly Asn Leu Lys Ile Cys Gly Ser 1 5 10 <210> SEQ ID NO 172 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 172 Ser Cys Val Arg Trp Gly Gln Leu Ser Ile Cys Gly Ser 1 5 10 <210> SEQ ID NO 173 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 173 Leu Lys Lys Phe Asn Ala Arg Arg Lys Leu Lys Gly Ala Ile Leu Thr 1 5 10 15 Thr Met Leu Ala Lys 20 <210> SEQ ID NO 174 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 174 Arg Arg Trp Lys Lys Asn Phe Ile Ala Val Ser Ala Ala Asn Arg Phe 1 5 10 15 Lys Lys <210> SEQ ID NO 175 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 175 Arg Lys Trp Gln Lys Thr Gly His Ala Val Arg Ala Ile Gly Arg Leu 1 5 10 15 Ser Ser <210> SEQ ID NO 176 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 176 Ile Asn Leu Lys Ala Leu Ala Ala Leu Ala Lys Lys Ile Leu 1 5 10 <210> SEQ ID NO 177 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 177 Lys Ile Trp Ser Ile Leu Ala Pro Leu Gly Thr Thr Leu Val Lys Leu 1 5 10 15 Val Ala <210> SEQ ID NO 178 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 178 Leu Lys Lys Leu Leu Lys Leu Leu Lys Lys Leu Leu Lys Leu 1 5 10 <210> SEQ ID NO 179 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 179 Leu Lys Trp Lys Lys Leu Leu Lys Leu Leu Lys Lys Leu Leu Lys Lys 1 5 10 15 Leu Leu <210> SEQ ID NO 180<211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 180 Ala Glu Trp Pro Ser Leu Thr Glu Ile Lys Thr Leu Ser His Phe Ser 1 5 10 15 Val <210> SEQ ID NO 181<211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 181 Ala Glu Trp Pro Ser Pro Thr Arg Val Ile Ser Thr Thr Tyr Phe Gly 1 5 10 15 Ser <210> SEQ ID NO 182 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 182 Ala Glu Leu Ala His Trp Pro Pro Val Lys Thr Val Leu Arg Ser Phe 1 5 10 15 Thr <210> SEQ ID NO 183 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 183 Ala Glu Gly Ser Trp Leu Gln Leu Leu Asn Leu Met Lys Gln Met Asn 1 5 10 15 Asn <210> SEQ ID NO 184 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CALMODULIN ANTAGONIST PEPTIDE <400> SEQUENCE: 184 Ala Glu Trp Pro Ser Leu Thr Glu Ile Lys 1 5 10 <210> SEQ ID NO 185 <211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VINCULIN-BINDING <400> SEQUENCE: 185 Ser Thr Gly Gly Phe Asp Asp Val Tyr Asp Trp Ala Arg Gly Val Ser 1 5 10 15 Ser Ala Leu Thr Thr Thr Leu Val Ala Thr Arg 20 25 <210> SEQ ID NO 186 <211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VINCULIN-BINDING <400> SEQUENCE: 186 Ser Thr Gly Gly Phe Asp Asp Val Tyr Asp Trp Ala Arg Arg Val Ser 1 5 10 15 Ser Ala Leu Thr Thr Thr Leu Val Ala Thr Arg 20 25 <210> SEQ ID NO 187 <211> LENGTH: 30 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VINCULIN-BINDING <400> SEQUENCE: 187 Ser Arg Gly Val Asn Phe Ser Glu Trp Leu Tyr Asp Met Ser Ala Ala 1 5 10 15 Met Lys Glu Ala Ser Asn Val Phe Pro Ser Arg Arg Ser Arg 20 25 30 <210> SEQ ID NO 188 <211> LENGTH: 30 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VINCULIN-BINDING <400> SEQUENCE: 188 Ser Ser Gln Asn Trp Asp Met Glu Ala Gly Val Glu Asp Leu Thr Ala 1 5 10 15 Ala Met Leu Gly Leu Leu Ser Thr Ile His Ser Ser Ser Arg 20 25 30 <210> SEQ ID NO 189 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VINCULIN-BINDING <400> SEQUENCE: 189 Ser Ser Pro Ser Leu Tyr Thr Gln Phe Leu Val Asn Tyr Glu Ser Ala 1 5 10 15 Ala Thr Arg Ile Gln Asp Leu Leu Ile Ala Ser Arg Pro Ser Arg 20 25 30 <210> SEQ ID NO 190 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VINCULIN-BINDING <400> SEQUENCE: 190 Ser Ser Thr Gly Trp Val Asp Leu Leu Gly Ala Leu Gln Arg Ala Ala 1 5 10 15 Asp Ala Thr Arg Thr Ser Ile Pro Pro Ser Leu Gln Asn Ser Arg 20 25 30 <210> SEQ ID NO 191 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VINCULIN-BINDING <400> SEQUENCE: 191 Asp Val Tyr Thr Lys Lys Glu Leu Ile Glu Cys Ala Arg Arg Val Ser 1 5 10 15 Glu Lys <210> SEQ ID NO 192 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: C4BP-BINDING <400> SEQUENCE: 192 Glu Lys Gly Ser Tyr Tyr Pro Gly Ser Gly Ile Ala Gln Phe His Ile 1 5 10 15 Asp Tyr Asn Asn Val Ser 20 <210> SEQ ID NO 193 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: C4BP-BINDING <400> SEQUENCE: 193 Ser Gly Ile Ala Gln Phe His Ile Asp Tyr Asn Asn Val Ser Ser Ala 1 5 10 15 Glu Gly Trp His Val Asn 20 <210> SEQ ID NO 194 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: C4BP-BINDING <400> SEQUENCE: 194 Leu Val Thr Val Glu Lys Gly Ser Tyr Tyr Pro Gly Ser Gly Ile Ala 1 5 10 15 Gln Phe His Ile Asp Tyr Asn Asn Val Ser Ser Ala Glu Gly Trp His 20 25 30 Val Asn <210> SEQ ID NO 195 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: C4BP-BINDING <400> SEQUENCE: 195 Ser Gly Ile Ala Gln Phe His Ile Asp Tyr Asn Asn Val Ser 1 5 10 <210> SEQ ID NO 196 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 196 Ala Glu Pro Met Pro His Ser Leu Asn Phe Ser Gln Tyr Leu Trp Tyr 1 5 10 15 Thr <210> SEQ ID NO 197 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 197 Ala Glu His Thr Tyr Ser Ser Leu Trp Asp Thr Tyr Ser Pro Leu Ala 1 5 10 15 Phe <210> SEQ ID NO 198 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 198 Ala Glu Leu Asp Leu Trp Met Arg His Tyr Pro Leu Ser Phe Ser Asn 1 5 10 15 Arg <210> SEQ ID NO 199 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 199 Ala Glu Ser Ser Leu Trp Thr Arg Tyr Ala Trp Pro Ser Met Pro Ser 1 5 10 15 Tyr <210> SEQ ID NO 200 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 200 Ala Glu Trp His Pro Gly Leu Ser Phe Gly Ser Tyr Leu Trp Ser Lys 1 5 10 15 Thr <210> SEQ ID NO 201 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 201 Ala Glu Pro Ala Leu Leu Asn Trp Ser Phe Phe Phe Asn Pro Gly Leu 1 5 10 15 His <210> SEQ ID NO 202 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 202 Ala Glu Trp Ser Phe Tyr Asn Leu His Leu Pro Glu Pro Gln Thr Ile 1 5 10 15 Phe <210> SEQ ID NO 203 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 203 Ala Glu Pro Leu Asp Leu Trp Ser Leu Tyr Ser Leu Pro Pro Leu Ala 1 5 10 15 Met <210> SEQ ID NO 204 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 204 Ala Glu Pro Thr Leu Trp Gln Leu Tyr Gln Phe Pro Leu Arg Leu Ser 1 5 10 15 Gly <210> SEQ ID NO 205 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 205 Ala Glu Ile Ser Phe Ser Glu Leu Met Trp Leu Arg Ser Thr Pro Ala 1 5 10 15 Phe <210> SEQ ID NO 206 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 206 Ala Glu Leu Ser Glu Ala Asp Leu Trp Thr Thr Trp Phe Gly Met Gly 1 5 10 15 Ser <210> SEQ ID NO 207 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 207 Ala Glu Ser Ser Leu Trp Arg Ile Phe Ser Pro Ser Ala Leu Met Met 1 5 10 15 Ser <210> SEQ ID NO 208 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 208 Ala Glu Ser Leu Pro Thr Leu Thr Ser Ile Leu Trp Gly Lys Glu Ser 1 5 10 15 Val <210> SEQ ID NO 209 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 209 Ala Glu Thr Leu Phe Met Asp Leu Trp His Asp Lys His Ile Leu Leu 1 5 10 15 Thr <210> SEQ ID NO 210 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 210 Ala Glu Ile Leu Asn Phe Pro Leu Trp His Glu Pro Leu Trp Ser Thr 1 5 10 15 Glu <210> SEQ ID NO 211 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 211 Ala Glu Ser Gln Thr Gly Thr Leu Asn Thr Leu Phe Trp Asn Thr Leu 1 5 10 15 Arg <210> SEQ ID NO 212 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Xaa is V, L, I, E, P, G, Y, M, T or D. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Xaa is Y, W or F. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Xaa is F, W or Y. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Xaa is P or Azetidine. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Xaa is S, A, V or L. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(8) <223> OTHER INFORMATION: Xaa is V, L, I or E. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Xaa is Q or P. <400> SEQUENCE: 212 Xaa Xaa Xaa Gln Xaa Tyr Xaa Xaa Xaa 1 5 <210> SEQ ID NO 213 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 213 Thr Ala Asn Val Ser Ser Phe Glu Trp Thr Pro Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 214 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 214 Ser Trp Thr Asp Tyr Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Ile Ser 1 5 10 15 Gly Leu <210> SEQ ID NO 215 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 215 Glu Thr Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 216 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 216 Glu Asn Thr Tyr Ser Pro Asn Trp Ala Asp Ser Met Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 217 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 217 Ser Val Gly Glu Asp His Asn Phe Trp Thr Ser Glu Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 218 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 218 Asp Gly Tyr Asp Arg Trp Arg Gln Ser Gly Glu Arg Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 219 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 219 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr 1 5 10 <210> SEQ ID NO 220 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 220 Phe Glu Trp Thr Pro Gly Tyr Trp Gln His Tyr 1 5 10 <210> SEQ ID NO 221 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 221 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 222 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, optionally acetlated at N terminus<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 222 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 223 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11, Xaa = azetidine<400> SEQUENCE: 223 Phe Glu Trp Thr Pro Gly Trp Pro Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 224 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 224 Phe Ala Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 225 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 225 Phe Glu Trp Ala Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 226 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 226 Phe Glu Trp Val Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 227 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 227 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 228 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, optionally acetylated at N terminus<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 228 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 229 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6 )..(6) <223> OTHER INFORMATION: Position 6, Xaa products = “MeGly”<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 229 Phe Glu Trp Thr Pro Xaa Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 230 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa = MeGly<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 230 Phe Glu Trp Thr Pro Xaa Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 231 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 231 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Pro Tyr 1 5 10 <210> SEQ ID NO 232 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 232 Phe Glu Trp Thr Pro Gly Trp Trp Gln Pro Tyr 1 5 10 <210> SEQ ID NO 233 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 233 Phe Glu Trp Thr Pro Asn Tyr Trp Gln Pro Tyr 1 5 10 <210> SEQ ID NO 234 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = pipecolic acid<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 234 Phe Glu Trp Thr Xaa Val Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 235 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = pipecolic acid<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 235 Phe Glu Trp Thr Xaa Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 236 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6 )..(6) <223> OTHER INFORMATION: Position 6, Xaa = Aib<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 236 Phe Glu Trp Thr Pro Xaa Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 237 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5 )..(5) <223> OTHER INFORMATION: Position 5, Xaa = MeGly<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 237 Phe Glu Trp Thr Xaa Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 238 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11, amino group added at C terminus<400> SEQUENCE: 238 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr 1 5 10 <210> SEQ ID NO 239 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11, amino group added at C-terminus<400> SEQUENCE: 239 Phe Glu Trp Thr Pro Gly Tyr Trp Gln His Tyr 1 5 10 <210> SEQ ID NO 240<211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is anazetidine residue Position 11 amino group added at C-terminus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 240 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 241<211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 optionally acetylated at N-terminus<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 241 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 242 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(8) <223> OTHER INFORMATION: Position 8, Xaa is a phyosphotyrosyl residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 242 Phe Glu Trp Thr Pro Gly Trp Xaa Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 243 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 243 Phe Ala Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 244 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 244 Phe Glu Trp Ala Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 245 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 245 Phe Glu Trp Val Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 246 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 246 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 247 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 acetylated at N-terminus<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 247 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 248 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, D amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 248 Phe Glu Trp Thr Pro Ala Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 249 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is a sarcosine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 249 Phe Glu Trp Thr Pro Xaa Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 250 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 250 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Pro Tyr 1 5 10 <210> SEQ ID NO 251 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 251 Phe Glu Trp Thr Pro Gly Trp Trp Gln Pro Tyr 1 5 10 <210> SEQ ID NO 252 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 252 Phe Glu Trp Thr Pro Asn Tyr Trp Gln Pro Tyr 1 5 10 <210> SEQ ID NO 253 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, D amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 253 Phe Glu Trp Thr Pro Val Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 254 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is a pipecolic acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 254 Phe Glu Trp Thr Xaa Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 255 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa = pipecolic acid<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 255 Phe Glu Trp Thr Pro Xaa Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 256 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = MeGly<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 256 Phe Glu Trp Thr Xaa Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 257 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 257 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 258 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a 1-naphthylalanine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 258 Xaa Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 259 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 259 Tyr Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 260 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 260 Phe Glu Trp Val Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 261 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, D amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 261 Phe Glu Trp Thr Pro Ser Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 262 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, D amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11 amino group added at C-terminus<400> SEQUENCE: 262 Phe Glu Trp Thr Pro Asn Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 263 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 263 Thr Lys Pro Arg 1 <210> SEQ ID NO 264 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 264 Arg Lys Ser Ser Lys 1 5 <210> SEQ ID NO 265 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 265 Arg Lys Gln Asp Lys 1 5 <210> SEQ ID NO 266 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 266 Asn Arg Lys Gln Asp Lys 1 5 <210> SEQ ID NO 267 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 267 Arg Lys Gln Asp Lys Arg 1 5 <210> SEQ ID NO 268 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 268 Glu Asn Arg Lys Gln Asp Lys Arg Phe 1 5 <210> SEQ ID NO 269 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 269 Val Thr Lys Phe Tyr Phe 1 5 <210> SEQ ID NO 270 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 270 Val Thr Lys Phe Tyr 1 5 <210> SEQ ID NO 271 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 271 Val Thr Asp Phe Tyr 1 5 <210> SEQ ID NO 272 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/ PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 272 Ser Gly Ser Gly Val Leu Lys Arg Pro Leu Pro Ile Leu Pro Val Thr 1 5 10 15 Arg <210> SEQ ID NO 273 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial SEquence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/ PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 273 Arg Trp Leu Ser Ser Arg Pro Leu Pro Pro Leu Pro Leu Pro Pro Arg 1 5 10 15 Thr <210> SEQ ID NO 274 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/ PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 274 Gly Ser Gly Ser Tyr Asp Thr Leu Ala Leu Pro Ser Leu Pro Leu His 1 5 10 15 Pro Met Ser Ser 20 <210> SEQ ID NO 275 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/ PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 275 Gly Ser Gly Ser Tyr Asp Thr Arg Ala Leu Pro Ser Leu Pro Leu His 1 5 10 15 Pro Met Ser Ser 20 <210> SEQ ID NO 276 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/ PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 276 Gly Ser Gly Ser Ser Gly Val Thr Met Tyr Pro Lys Leu Pro Pro His 1 5 10 15 Trp Ser Met Ala 20 <210> SEQ ID NO 277 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/ PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 277 Gly Ser Gly Ser Ser Gly Val Arg Met Tyr Pro Lys Leu Pro Pro His 1 5 10 15 Trp Ser Met Ala 20 <210> SEQ ID NO 278 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/ PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 278 Gly Ser Gly Ser Ser Ser Met Arg Met Val Pro Thr Ile Pro Gly Ser 1 5 10 15 Ala Lys His Gly 20 <210> SEQ ID NO 279 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTI-HBV <400> SEQUENCE: 279 Leu Leu Gly Arg Met Lys 1 5 <210> SEQ ID NO 280 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTI-HBV <400> SEQUENCE: 280 Ala Leu Leu Gly Arg Met Lys Gly 1 5 <210> SEQ ID NO 281 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTI-HBV <400> SEQUENCE: 281 Leu Asp Pro Ala Phe Arg 1 5 <210> SEQ ID NO 282 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 282 Arg Pro Leu Pro Pro Leu Pro 1 5 <210> SEQ ID NO 283 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 283 Arg Glu Leu Pro Pro Leu Pro 1 5 <210> SEQ ID NO 284 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 284 Ser Pro Leu Pro Pro Leu Pro 1 5 <210> SEQ ID NO 285 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 285 Gly Pro Leu Pro Pro Leu Pro 1 5 <210> SEQ ID NO 286 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 286 Arg Pro Leu Pro Ile Pro Pro 1 5 <210> SEQ ID NO 287 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 287 Arg Pro Leu Pro Ile Pro Pro 1 5 <210> SEQ ID NO 288 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 288 Arg Arg Leu Pro Pro Thr Pro 1 5 <210> SEQ ID NO 289 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 289 Arg Gln Leu Pro Pro Thr Pro 1 5 <210> SEQ ID NO 290 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 290 Arg Pro Leu Pro Ser Arg Pro 1 5 <210> SEQ ID NO 291 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 291 Arg Pro Leu Pro Thr Arg Pro 1 5 <210> SEQ ID NO 292 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 292 Ser Arg Leu Pro Pro Leu Pro 1 5 <210> SEQ ID NO 293 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 293 Arg Ala Leu Pro Ser Pro Pro 1 5 <210> SEQ ID NO 294 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 294 Arg Arg Leu Pro Arg Thr Pro 1 5 <210> SEQ ID NO 295 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 295 Arg Pro Val Pro Pro Ile Thr 1 5 <210> SEQ ID NO 296 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 296 Ile Leu Ala Pro Pro Val Pro 1 5 <210> SEQ ID NO 297 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 297 Arg Pro Leu Pro Met Leu Pro 1 5 <210> SEQ ID NO 298 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 298 Arg Pro Leu Pro Ile Leu Pro 1 5 <210> SEQ ID NO 299 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 299 Arg Pro Leu Pro Ser Leu Pro 1 5 <210> SEQ ID NO 300<211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 300 Arg Pro Leu Pro Ser Leu Pro 1 5 <210> SEQ ID NO 301<211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 301 Arg Pro Leu Pro Met Ile Pro 1 5 <210> SEQ ID NO 302 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 302 Arg Pro Leu Pro Leu Ile Pro 1 5 <210> SEQ ID NO 303 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 303 Arg Pro Leu Pro Pro Thr Pro 1 5 <210> SEQ ID NO 304 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 304 Arg Ser Leu Pro Pro Leu Pro 1 5 <210> SEQ ID NO 305 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 305 Arg Pro Gln Pro Pro Pro Pro 1 5 <210> SEQ ID NO 306 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <400> SEQUENCE: 306 Arg Gln Leu Pro Ile Pro Pro 1 5 <210> SEQ ID NO 307 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 2, 3)..(11) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 307 Xaa Xaa Xaa Arg Pro Leu Pro Pro Leu Pro Xaa Pro 1 5 10 <210> SEQ ID NO 308 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 2, 3, 11)..(12) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 308 Xaa Xaa Xaa Arg Pro Leu Pro Pro Ile Pro Xaa Xaa 1 5 10 <210> SEQ ID NO 309 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 2, 3, 11,)..(12) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 309 Xaa Xaa Xaa Arg Pro Leu Pro Pro Leu Pro Xaa Xaa 1 5 10 <210> SEQ ID NO 310 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3, 10)..(11) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 310 Arg Xaa Xaa Arg Pro Leu Pro Pro Leu Pro Xaa Pro 1 5 10 <210> SEQ ID NO 311 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(3) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 311 Arg Xaa Xaa Arg Pro Leu Pro Pro Leu Pro Pro Pro 1 5 10 <210> SEQ ID NO 312 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(12) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 312 Pro Pro Pro Tyr Pro Pro Pro Pro Ile Pro Xaa Xaa 1 5 10 <210> SEQ ID NO 313 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(12) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 313 Pro Pro Pro Tyr Pro Pro Pro Pro Val Pro Xaa Xaa 1 5 10 <210> SEQ ID NO 314 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3)..(8) <223> OTHER INFORMATION: Xaa (Pos2, 3, 8) is any amino acid <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Xaa (Pos 9) represents an aliphatic amino acid residue <400> SEQUENCE: 314 Leu Xaa Xaa Arg Pro Leu Pro Xaa Xaa Pro 1 5 10 <210> SEQ ID NO 315 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is an aliphatic amino acidresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3)..(8) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 315 Xaa Xaa Xaa Arg Pro Leu Pro Xaa Leu Pro 1 5 10 <210> SEQ ID NO 316 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa is any amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is an aromatic amino acidresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Position 9, Xaa is an aliphatic amino acidprovided that eithresidue <400> SEQUENCE: 316 Pro Pro Xaa Xaa Tyr Pro Pro Pro Xaa Pro 1 5 10 <210> SEQ ID NO 317 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a basic amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is an aliphatic amino acidresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(9) <223> OTHER INFORMATION: Positions 6 & 9, Xaa is any amino acid residue<400> SEQUENCE: 317 Xaa Pro Pro Xaa Pro Xaa Lys Pro Xaa Trp Leu 1 5 10 <210> SEQ ID NO 318 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3, 4)..(6) <223> OTHER INFORMATION: Positions acid residue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(8) <223> OTHER INFORMATION: Position 8, Xaa is a basic amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is any amino acid residue<400> SEQUENCE: 318 Arg Pro Xaa Xaa Pro Xaa Arg Xaa Ser Xaa Pro 1 5 10 <210> SEQ ID NO 319 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(9) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 319 Pro Pro Val Pro Pro Arg Pro Xaa Xaa Thr Leu 1 5 10 <210> SEQ ID NO 320 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 3)..(6) <223> OTHER INFORMATION: Positions acid residue <400> SEQUENCE: 320 Xaa Pro Xaa Leu Pro Xaa Lys 1 5 <210> SEQ ID NO 321 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SH3 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a basic amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Position 2, Xaa is an aromatic amino acidresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(8) <223> OTHER INFORMATION: Positions 4 & 8, Xaa is any amino acid residue<400> SEQUENCE: 321 Xaa Xaa Asp Xaa Pro Leu Pro Xaa Leu Pro 1 5 10 <210> SEQ ID NO 322 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INHIBITION OF PLATELET AGGREGATION <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(3) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 322 Cys Xaa Xaa Arg Gly Asp Cys 1 5 <210> SEQ ID NO 323 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SRC ANTAGONIST <400> SEQUENCE: 323 Arg Pro Leu Pro Pro Leu Pro 1 5 <210> SEQ ID NO 324 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SRC ANTAGONIST <400> SEQUENCE: 324 Pro Pro Val Pro Pro Arg 1 5 <210> SEQ ID NO 325 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTI-CANCER (PARTICULARLY FOR SARCOMAS) <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 3, 5, 7, 8, 10)..(11) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 325 Xaa Phe Xaa Asp Xaa Trp Xaa Xaa Leu Xaa Xaa 1 5 10 <210> SEQ ID NO 326 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P16-MIMETIC <400> SEQUENCE: 326 Lys Ala Cys Arg Arg Leu Phe Gly Pro Val Asp Ser Glu Gln Leu Ser 1 5 10 15 Arg Asp Cys Asp 20 <210> SEQ ID NO 327 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P16-MIMETIC <400> SEQUENCE: 327 Arg Glu Arg Trp Asn Phe Asp Phe Val Thr Glu Thr Pro Leu Glu Gly 1 5 10 15 Asp Phe Ala Trp 20 <210> SEQ ID NO 328 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P16-MIMETIC <400> SEQUENCE: 328 Lys Arg Arg Gln Thr Ser Met Thr Asp Phe Tyr His Ser Lys Arg Arg 1 5 10 15 Leu Ile Phe Ser 20 <210> SEQ ID NO 329 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P16-MIMETIC <400> SEQUENCE: 329 Thr Ser Met Thr Asp Phe Tyr His Ser Lys Arg Arg Leu Ile Phe Ser 1 5 10 15 Lys Arg Lys Pro 20 <210> SEQ ID NO 330 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P16-MIMETIC <400> SEQUENCE: 330 Arg Arg Leu Ile Phe 1 5 <210> SEQ ID NO 331 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P16-MIMETIC <400> SEQUENCE: 331 Lys Arg Arg Gln Thr Ser Ala Thr Asp Phe Tyr His Ser Lys Arg Arg 1 5 10 15 Leu Ile Phe Ser Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met 20 25 30 Lys Trp Lys Lys 35 <210> SEQ ID NO 332 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P16-MIMETIC <400> SEQUENCE: 332 Lys Arg Arg Leu Ile Phe Ser Lys Arg Gln Ile Lys Ile Trp Phe Gln 1 5 10 15 Asn Arg Arg Met Lys Trp Lys Lys 20 <210> SEQ ID NO 333 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: PREFERRED LINKER <400> SEQUENCE: 333 Gly Gly Gly Lys Gly Gly Gly Gly 1 5 <210> SEQ ID NO 334 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: PREFERRED LINKER <400> SEQUENCE: 334 Gly Gly Gly Asn Gly Ser Gly Gly 1 5 <210> SEQ ID NO 335 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: PREFERRED LINKER <400> SEQUENCE: 335 Gly Gly Gly Cys Gly Gly Gly Gly 1 5 <210> SEQ ID NO 336 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: PREFERRED LINKER <400> SEQUENCE: 336 Gly Pro Asn Gly Gly 1 5 <210> SEQ ID NO 337 <211> LENGTH: 41 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Fc domain attached at Position 1 of theN-terminus <400> SEQUENCE: 337 Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala 1 5 10 15 Ala Arg Ala Gly Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr 20 25 30 Leu Arg Gln Trp Leu Ala Ala Arg Ala 35 40 <210> SEQ ID NO 338 <211> LENGTH: 41 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (41)..(41) <223> OTHER INFORMATION: Fc domain attached at Position 41 of the C-terminus <400> SEQUENCE: 338 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala Gly Gly Gly Gly Gly 35 40 <210> SEQ ID NO 339 <211> LENGTH: 49 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Fc domain attached at Position 1 of theN-terminus <400> SEQUENCE: 339 Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu 1 5 10 15 Thr Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Gly Thr 20 25 30 Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly 35 40 45 Gly <210> SEQ ID NO 340 <211> LENGTH: 49 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (49)..(49) <223> OTHER INFORMATION: Fc domain attached at Position 49 of theC-terminus <400> SEQUENCE: 340 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His Phe 20 25 30 Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly Gly 35 40 45 Gly <210> SEQ ID NO 341 <211> LENGTH: 28 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 341 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Ile Glu 1 5 10 15 Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 20 25 <210> SEQ ID NO 342 <211> LENGTH: 29 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 342 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Ile 1 5 10 15 Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 20 25 <210> SEQ ID NO 343 <211> LENGTH: 30 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 343 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 20 25 30 <210> SEQ ID NO 344 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 344 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 20 25 30 <210> SEQ ID NO 345 <211> LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 345 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 20 25 30 <210> SEQ ID NO 346 <211> LENGTH: 33 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 346 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg 20 25 30 Ala <210> SEQ ID NO 347 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 347 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala 20 25 30 Arg Ala <210> SEQ ID NO 348 <211> LENGTH: 35 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 348 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala 20 25 30 Ala Arg Ala 35 <210> SEQ ID NO 349 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 349 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 350 <211> LENGTH: 37 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 350 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp 20 25 30 Leu Ala Ala Arg Ala 35 <210> SEQ ID NO 351 <211> LENGTH: 38 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 351 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln 20 25 30 Trp Leu Ala Ala Arg Ala 35 <210> SEQ ID NO 352 <211> LENGTH: 42 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 352 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro 20 25 30 Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 35 40 <210> SEQ ID NO 353 <211> LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 353 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Pro 1 5 10 15 Asn Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 20 25 30 <210> SEQ ID NO 354 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 354 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 355 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 355 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 356 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 356 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 357 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 357 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Lys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 358 <211> LENGTH: 37 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (19)..(19) <223> OTHER INFORMATION: Position 19, Xaa = bromoacetyl<400> SEQUENCE: 358 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Lys Xaa Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp 20 25 30 Leu Ala Ala Arg Ala 35 <210> SEQ ID NO 359 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 359 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Cys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 360<211> LENGTH: 37 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (19)..(19) <223> OTHER INFORMATION: Position 19, Xaa = Poly(ethylene glycol)<400> SEQUENCE: 360 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Lys Xaa Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp 20 25 30 Leu Ala Ala Arg Ala 35 <210> SEQ ID NO 361<211> LENGTH: 37 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (19)..(19) <223> OTHER INFORMATION: Position 19, Xaa = Poly(ethylene glycol)<400> SEQUENCE: 361 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Cys Xaa Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp 20 25 30 Leu Ala Ala Arg Ala 35 <210> SEQ ID NO 362 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 362 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Asn Gly Ser Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 363 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC PEPTIDES <400> SEQUENCE: 363 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Cys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 364 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <400> SEQUENCE: 364 aaaaaaggat cctcgagatt aagcacgagc agccagccac tgacgcagag tcggacc 57 <210> SEQ ID NO 365 <211> LENGTH: 39 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <400> SEQUENCE: 365 aaaggtggag gtggtggtat cgaaggtccg actctgcgt 39 <210> SEQ ID NO 366 <211> LENGTH: 42 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <400> SEQUENCE: 366 cagtggctgg ctgctcgtgc ttaatctcga ggatcctttt tt 42<210> SEQ ID NO 367 <211> LENGTH: 81 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)..(60) <223> OTHER INFORMATION: <400> SEQUENCE: 367 aaa ggt gga ggt ggt ggt atc gaa ggt ccg act ctg cgt cag tgg ctg 48 Lys Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 1 5 10 15 gct gct cgt gct taatctcgag gatccttttt t 81Ala Ala Arg Ala 20 <210> SEQ ID NO 368 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <400> SEQUENCE: 368 Lys Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 1 5 10 15 Ala Ala Arg Ala 20 <210> SEQ ID NO 369 <211> LENGTH: 22 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <400> SEQUENCE: 369 aacataagta cctgtaggat cg 22<210> SEQ ID NO 370 <211> LENGTH: 52 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP <400> SEQUENCE: 370 ttcgatacca ccacctccac ctttacccgg agacagggag aggctcttct gc 52 <210> SEQ ID NO 371 <211> LENGTH: 60 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP-TMP <400> SEQUENCE: 371 aaaggtggag gtggtggtat cgaaggtccg actctgcgtc agtggctggc tgctcgtgct 60<210> SEQ ID NO 372 <211> LENGTH: 48 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP-TMP <400> SEQUENCE: 372 acctccacca ccagcacgag cagccagcca ctgacgcaga gtcggacc 48 <210> SEQ ID NO 373 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP-TMP <400> SEQUENCE: 373 ggtggtggag gtggcggcgg aggtattgag ggcccaaccc ttcgccaatg gcttgcagca 60cgcgca 66 <210> SEQ ID NO 374 <211> LENGTH: 76 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP-TMP <400> SEQUENCE: 374 Ala Ala Ala Ala Ala Ala Ala Gly Gly Ala Thr Cys Cys Thr Cys Gly 1 5 10 15 Ala Gly Ala Thr Thr Ala Thr Gly Cys Gly Cys Gly Thr Gly Cys Thr 20 25 30 Gly Cys Ala Ala Gly Cys Cys Ala Thr Thr Gly Gly Cys Gly Ala Ala 35 40 45 Gly Gly Gly Thr Thr Gly Gly Gly Cys Cys Cys Thr Cys Ala Ala Thr 50 55 60 Ala Cys Cys Thr Cys Cys Gly Cys Cys Gly Cys Cys 65 70 75 <210> SEQ ID NO 375 <211> LENGTH: 126 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP-TMP <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)..(126) <223> OTHER INFORMATION: <400> SEQUENCE: 375 aaa ggt gga ggt ggt ggt atc gaa ggt ccg act ctg cgt cag tgg ctg 48 Lys Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 1 5 10 15 gct gct cgt gct ggt ggt gga ggt ggc ggc gga ggt att gag ggc cca 96 Ala Ala Arg Ala Gly Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro 20 25 30 acc ctt cgc caa tgg ctt gca gca cgc gca 126 Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 35 40 <210> SEQ ID NO 376 <211> LENGTH: 42 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TMP-TMP <400> SEQUENCE: 376 Lys Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 1 5 10 15 Ala Ala Arg Ala Gly Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro 20 25 30 Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala 35 40 <210> SEQ ID NO 377 <211> LENGTH: 39 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 377 Thr Thr Thr Thr Thr Thr Cys Ala Thr Ala Thr Gly Ala Thr Cys Gly 1 5 10 15 Ala Ala Gly Gly Thr Cys Cys Gly Ala Cys Thr Cys Thr Gly Cys Gly 20 25 30 Thr Cys Ala Gly Thr Gly Gly 35 <210> SEQ ID NO 378 <211> LENGTH: 48 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 378 Ala Gly Cys Ala Cys Gly Ala Gly Cys Ala Gly Cys Cys Ala Gly Cys 1 5 10 15 Cys Ala Cys Thr Gly Ala Cys Gly Cys Ala Gly Ala Gly Thr Cys Gly 20 25 30 Gly Ala Cys Cys Thr Thr Cys Gly Ala Thr Cys Ala Thr Ala Thr Gly 35 40 45 <210> SEQ ID NO 379 <211> LENGTH: 45 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 379 ctggctgctc gtgctggtgg aggcggtggg gacaaaactc acaca 45<210> SEQ ID NO 380 <211> LENGTH: 51 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 380 ctggctgctc gtgctggcgg tggtggcgga gggggtggca ttgagggccc a 51 <210> SEQ ID NO 381 <211> LENGTH: 54 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 381 aagccattgg cgaagggttg ggccctcaat gccaccccct ccgccaccac cgcc 54 <210> SEQ ID NO 382 <211> LENGTH: 54 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 382 acccttcgcc aatggcttgc agcacgcgca gggggaggcg gtggggacaa aact 54 <210> SEQ ID NO 383 <211> LENGTH: 27 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 383 cccaccgcct ccccctgcgc gtgctgc 27 <210> SEQ ID NO 384 <211> LENGTH: 189 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (10)..(180) <223> OTHER INFORMATION: <400> SEQUENCE: 384 ttttttcat atg atc gaa ggt ccg act ctg cgt cag tgg ctg gct gct cgt 51 Met Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg 1 5 10 gct ggc ggt ggt ggc gga ggg ggt ggc att gag ggc cca acc ctt cgc 99 Ala Gly Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg 15 20 25 30 caa tgg ctg gct gct cgt gct ggt gga ggc ggt ggg gac aaa act ctg 147 Gln Trp Leu Ala Ala Arg Ala Gly Gly Gly Gly Gly Asp Lys Thr Leu 35 40 45 gct gct cgt gct ggt gga ggc ggt ggg gac aaa actcacaca 189 Ala Ala Arg Ala Gly Gly Gly Gly Gly Asp Lys 50 55 <210> SEQ ID NO 385 <211> LENGTH: 57 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TMP-TMP-Fc <400> SEQUENCE: 385 Met Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp 20 25 30 Leu Ala Ala Arg Ala Gly Gly Gly Gly Gly Asp Lys Thr Leu Ala Ala 35 40 45 Arg Ala Gly Gly Gly Gly Gly Asp Lys 50 55 <210> SEQ ID NO 386 <211> LENGTH: 141 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: pAMG21 <400> SEQUENCE: 386 ctaattccgc tctcacctac caaacaatgc ccccctgcaa aaaataaatt catataaaaa 60acatacagat aaccatctgc ggtgataaat tatctctggc ggtgttgaca taaataccac 120tggcggtgat actgagcaca t 141 <210> SEQ ID NO 387 <211> LENGTH: 55 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: pAMG21 <400> SEQUENCE: 387 cgatttgatt ctagaaggag gaataacata tggttaacgc gttggaattc ggtac 55<210> SEQ ID NO 388 <211> LENGTH: 872 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: GM221 <400> SEQUENCE: 388 ttattttcgt gcggccgcac cattatcacc gccagaggta aactagtcaa cacgcacggt 60 gttagatatt tatcccttgc ggtgatagat tgagcacatc gatttgattc tagaaggagg 120 gataatatat gagcacaaaa aagaaaccat taacacaaga gcagcttgag gacgcacgtc 180 gccttaaagc aatttatgaa aaaaagaaaa atgaacttgg cttatcccag gaatctgtcg 240cagacaagat ggggatgggg cagtcaggcg ttggtgcttt atttaatggc atcaatgcat 300 taaatgctta taacgccgca ttgcttacaa aaattctcaa agttagcgtt gaagaattta 360 gcccttcaat cgccagagaa tctacgagat gtatgaagcg gttagtatgc agccgtcact 420tagaagtgag tatgagtacc ctgttttttc tcatgttcag gcagggatgt tctcacctaa 480 gcttagaacc tttaccaaag gtgatgcgga gagatgggta agcacaacca aaaaagccag 540 tgattctgca ttctggcttg aggttgaagg taattccatg accgcaccaa caggctccaa 600 gccaagcttt cctgacggaa tgttaattct cgttgaccct gagcaggctg ttgagccagg 660 tgatttctgc atagccagac ttgggggtga tgagtttacc ttcaagaaac tgatcaggga 720 tagcggtcag gtgtttttac aaccactaaa cccacagtac ccaatgatcc catgcaatga 780 gagttgttcc gttgtgggga aagttatcgc tagtcagtgg cctgaagaga cgtttggctg 840atagactagt ggatccacta gtgtttctgc cc 872 <210> SEQ ID NO 389 <211> LENGTH: 1197 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: GM221 <400> SEQUENCE: 389 ggcggaaacc gacgtccatc gaatggtgca aaacctttcg cggtatggca tgatagcgcc 60 cggaagagag tcaattcagg gtggtgaatg tgaaaccagt aacgttatac gatgtcgcag 120 agtatgccgg tgtctcttat cagaccgttt cccgcgtggt gaaccaggcc agccacgttt 180 ctgcgaaaac gcgggaaaaa gtcgaagcgg cgatggcgga gctgaattac attcccaacc 240 gcgtggcaca acaactggcg ggcaaacagt cgctcctgat tggcgttgcc acctccagtc 300 tggccctgca cgcgccgtcg caaattgtcg cggcgattaa atctcgcgcc gatcaactgg 360 gtgccagcgt ggtggtgtcg atggtagaac gaagcggcgt cgaagcctgt aaagcggcgg 420 tgcacaatct tctcgcgcaa cgcgtcagtg ggctgatcat taactatccg ctggatgacc 480 aggatgccat tgctgtggaa gctgcctgca ctaatgttcc ggcgttattt cttgatgtct 540ctgaccagac acccatcaac agtattattt tctcccatga agacggtacg cgactgggcg 600tggagcatct ggtcgcattg ggtcaccagc aaatcgcgct gttagcgggc ccattaagtt 660 ctgtctcggc gcgtctgcgt ctggctggct ggcataaata tctcactcgc aatcaaattc 720agccgatagc ggaacgggaa ggcgactgga gtgccatgtc cggttttcaa caaaccatgc 780 aaatgctgaa tgagggcatc gttcccactg cgatgctggt tgccaacgat cagatggcgc 840tgggcgcaat gcgcgccatt accgagtccg ggctgcgcgt tggtgcggat atctcggtag 900 tgggatacga cgataccgaa gacagctcat gttatatccc gccgttaacc accatcaaac 960 aggattttcg cctgctgggg caaaccagcg tggaccgctt gctgcaactc tctcagggcc 1020 aggcggtgaa gggcaatcag ctgttgcccg tctcactggt gaaaagaaaa accaccctgg 1080 cgcccaatac gcaaaccgcc tctccccgcg cgttggccga ttcattaatg cagctggcac 1140 gacaggtttc ccgactggaa agcggacagt aaggtaccat aggatccagg cacagga 1197 <210> SEQ ID NO 390 <211> LENGTH: 61 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 390 tatgaaaggt ggaggtggtg gtggaggtac ttactcttgc cacttcggcc cgctgacttg 60 g 61<210> SEQ ID NO 391 <211> LENGTH: 72 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 391 cggtttgcaa acccaagtca gcgggccgaa gtggcaagag taagtacctc caccaccacc 60tccacctttc at 72 <210> SEQ ID NO 392 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 392 gtttgcaaac cgcagggtgg cggcggcggc ggcggtggta cctattcctg tcatttt 57 <210> SEQ ID NO 393 <211> LENGTH: 60 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 393 ccaggtcagc gggccaaaat gacaggaata ggtaccaccg ccgccgccgc cgccaccctg 60<210> SEQ ID NO 394 <211> LENGTH: 118 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (2)..(118) <223> OTHER INFORMATION: <400> SEQUENCE: 394 t atg aaa ggt gga ggt ggt ggt gga ggt act tac tct tgc cac ttc ggc 49Met Lys Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His Phe Gly 1 5 10 15 ccg ctg act tgg gtt tgc aaa ccg cag ggt ggc ggc ggc ggc ggc ggt 97 Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly 20 25 30 ggt acc tat tcc tgt cat ttt 118 Gly Thr Tyr Ser Cys His Phe 35 <210> SEQ ID NO 395 <211> LENGTH: 39 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 395 Met Lys Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His Phe Gly 1 5 10 15 Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly 20 25 30 Gly Thr Tyr Ser Cys His Phe 35 <210> SEQ ID NO 396 <211> LENGTH: 61 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 396 gcagaagagc ctctccctgt ctccgggtaa aggtggaggt ggtggtggag gtacttactc 60 t 61<210> SEQ ID NO 397 <211> LENGTH: 40 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 397 ctaattggat ccacgagatt aaccaccctg cggtttgcaa 40<210> SEQ ID NO 398 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 398 Gly Glu Arg Trp Cys Phe Asp Gly Pro Leu Thr Trp Val Cys Gly Glu 1 5 10 15 Glu Ser <210> SEQ ID NO 399 <211> LENGTH: 61 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP <400> SEQUENCE: 399 agagtaagta cctccaccac cacctccacc tttacccgga gacagggaga ggctcttctg 60 c 61<210> SEQ ID NO 400 <211> LENGTH: 61 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <400> SEQUENCE: 400 ggcccgctga cctgggtatg taagccacaa gggggtgggg gaggcggggg gtaatctcga 60 g 61<210> SEQ ID NO 401 <211> LENGTH: 50 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <400> SEQUENCE: 401 gatcctcgag attacccccc gcctccccca cccccttgtg gcttacatac 50<210> SEQ ID NO 402 <211> LENGTH: 118 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)..(108) <223> OTHER INFORMATION: <400> SEQUENCE: 402 gtt tgc aaa ccg cag ggt ggc ggc ggc ggc ggc ggt ggt acc tat tcc 48 Val Cys Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser 1 5 10 15 tgt cat ttt ggc ccg ctg acc tgg gta tgt aag cca caa ggg ggt ggg 96 Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly 20 25 30 gga ggc ggg ggg taatctcgag 118 Gly Gly Gly Gly 35 <210> SEQ ID NO 403 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <400> SEQUENCE: 403 Val Cys Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser 1 5 10 15 Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly 20 25 30 Gly Gly Gly Gly 35 <210> SEQ ID NO 404 <211> LENGTH: 39 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <400> SEQUENCE: 404 ttatttcata tgaaaggtgg taactattcc tgtcatttt 39 <210> SEQ ID NO 405 <211> LENGTH: 43 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <400> SEQUENCE: 405 tggacatgtg tgagttttgt cccccccgcc tcccccaccc cct 43 <210> SEQ ID NO 406 <211> LENGTH: 43 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <400> SEQUENCE: 406 agggggtggg ggaggcgggg gggacaaaac tcacacatgt cca 43 <210> SEQ ID NO 407 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-Fc <400> SEQUENCE: 407 gttattgctc agcggtggca 20<210> SEQ ID NO 408 <211> LENGTH: 60 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 408 ttttttatcg atttgattct agatttgagt tttaactttt agaaggagga ataaaatatg 60<210> SEQ ID NO 409 <211> LENGTH: 41 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 409 taaaagttaa aactcaaatc tagaatcaaa tcgataaaaa a 41 <210> SEQ ID NO 410 <211> LENGTH: 51 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 410 ggaggtactt actcttgcca cttcggcccg ctgacttggg tttgcaaacc g 51 <210> SEQ ID NO 411 <211> LENGTH: 55 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 411 agtcagcggg ccgaagtggc aagagtaagt acctcccata ttttattcct ccttc 55<210> SEQ ID NO 412 <211> LENGTH: 60 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 412 cagggtggcg gcggcggcgg cggtggtacc tattcctgtc attttggccc gctgacctgg 60<210> SEQ ID NO 413 <211> LENGTH: 60 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 413 aaaatgacag gaataggtac caccgccgcc gccgccgcca ccctgcggtt tgcaaaccca 60<210> SEQ ID NO 414 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 414 gtatgtaagc cacaaggggg tgggggaggc gggggggaca aaactcacac atgtcca 57 <210> SEQ ID NO 415 <211> LENGTH: 60 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 415 agttttgtcc cccccgcctc ccccaccccc ttgtggctta catacccagg tcagcgggcc 60<210> SEQ ID NO 416 <211> LENGTH: 228 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (58)..(228) <223> OTHER INFORMATION: <400> SEQUENCE: 416 ttttttatcg atttgattct agatttgagt tttaactttt agaaggagga ataaaat 57 atg gga ggt act tac tct tgc cac ttc ggc ccg ctg act tgg gtt tgc 105 Met Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys 1 5 10 15 aaa ccg cag ggt ggc ggc ggc ggc ggc ggt ggt acc tat tcc tgt cat 153 Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His 20 25 30 ttt ggc ccg ctg acc tgg gta tgt aag cca caa ggg ggt ggg gga ggc 201 Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly 35 40 45 ggg ggg gac aaa act cac aca tgt cca 228 Gly Gly Asp Lys Thr His Thr Cys Pro 50 55 <210> SEQ ID NO 417 <211> LENGTH: 57 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EMP-EMP-Fc <400> SEQUENCE: 417 Met Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys 1 5 10 15 Lys Pro Gln Gly Gly Gly Gly Gly Gly Gly Gly Thr Tyr Ser Cys His 20 25 30 Phe Gly Pro Leu Thr Trp Val Cys Lys Pro Gln Gly Gly Gly Gly Gly 35 40 45 Gly Gly Asp Lys Thr His Thr Cys Pro 50 55 <210> SEQ ID NO 418 <211> LENGTH: 40 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-EMP-EMP <400> SEQUENCE: 418 ctaattggat cctcgagatt aacccccttg tggcttacat 40 <210> SEQ ID NO 419 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 3, 9, 14, 15)..(16) <223> OTHER INFORMATION: Xaa ( Positions any one of the 20 L-amino acids <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Xaa can be R, H, L or W <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Xaa can be M, F or I <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (12)..(12) <223> OTHER INFORMATION: Xaa can be D, E, I, L or V <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (13)..(13) <223> OTHER INFORMATION: Xaa can be C, A, a-amino-y-bromobutyric acid or Hoc <400> SEQUENCE: 419 Xaa Tyr Xaa Xaa Xaa Xaa Gly Pro Xaa Thr Trp Xaa Xaa Xaa Xaa Xaa 1 5 10 15 <210> SEQ ID NO 420<211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 3, 5, 6, 9, 12, 14, 15)..(16) <223> OTHER INFORMATION: Xaa = any amino acid residue <400> SEQUENCE: 420 Xaa Tyr Xaa Cys Xaa Xaa Gly Pro Xaa Thr Trp Xaa Cys Xaa Xaa Xaa 1 5 10 15 <210> SEQ ID NO 421<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Xaa can be R, H, L, or W <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Xaa can be M, F, or I <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Xaa is independently selected from any one of the 20 genetically coded L-amino acids or the steroisomeric D-amino acids <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Xaa can be D, E, I, L, or V. <400> SEQUENCE: 421 Cys Xaa Xaa Gly Pro Xaa Thr Trp Xaa Cys 1 5 10 <210> SEQ ID NO 422 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 422 Gly Gly Thr Tyr Ser Cys His Gly Pro Leu Thr Trp Val Cys Lys Pro 1 5 10 15 Gln Gly Gly <210> SEQ ID NO 423 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 423 Val Gly Asn Tyr Met Ala His Met Gly Pro Ile Thr Trp Val Cys Arg 1 5 10 15 Pro Gly Gly <210> SEQ ID NO 424 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 424 Gly Gly Pro His His Val Tyr Ala Cys Arg Met Gly Pro Leu Thr Trp 1 5 10 15 Ile Cys <210> SEQ ID NO 425 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 425 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln <210> SEQ ID NO 426 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 426 Gly Gly Leu Tyr Ala Cys His Met Gly Pro Met Thr Trp Val Cys Gln 1 5 10 15 Pro Leu Arg Gly 20 <210> SEQ ID NO 427 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 427 Thr Ile Ala Gln Tyr Ile Cys Tyr Met Gly Pro Glu Thr Trp Glu Cys 1 5 10 15 Arg Pro Ser Pro Lys Ala 20 <210> SEQ ID NO 428 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 428 Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 <210> SEQ ID NO 429 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 429 Tyr Cys His Phe Gly Pro Leu Thr Trp Val Cys 1 5 10 <210> SEQ ID NO 430 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 430 Ala Glu Pro Val Tyr Gln Tyr Glu Leu Asp Ser Tyr Leu Arg Ser Tyr 1 5 10 15 Tyr <210> SEQ ID NO 431 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 431 Ala Glu Leu Asp Leu Ser Thr Phe Tyr Asp Ile Gln Tyr Leu Leu Arg 1 5 10 15 Thr <210> SEQ ID NO 432 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 432 Ala Glu Phe Phe Lys Leu Gly Pro Asn Gly Tyr Val Tyr Leu His Ser 1 5 10 15 Ala <210> SEQ ID NO 433 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4, 5)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 433 Phe Lys Leu Xaa Xaa Xaa Gly Tyr Val Tyr Leu 1 5 10 <210> SEQ ID NO 434 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <400> SEQUENCE: 434 Ala Glu Ser Thr Tyr His His Leu Ser Leu Gly Tyr Met Tyr Thr Leu 1 5 10 15 Asn <210> SEQ ID NO 435 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: UKR ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3, 5)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 435 Tyr His Xaa Leu Xaa Xaa Gly Tyr Met Tyr Thr 1 5 10 <210> SEQ ID NO 436 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 436 Arg Asn Arg Gln Lys Thr 1 5 <210> SEQ ID NO 437 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 437 Arg Asn Arg Gln 1 <210> SEQ ID NO 438 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 438 Arg Asn Arg Gln Lys 1 5 <210> SEQ ID NO 439 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 439 Asn Arg Gln Lys Thr 1 5 <210> SEQ ID NO 440 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MAST CELL ANTAGONISTS/PROTEASE INHIBITOR PEPTIDE <400> SEQUENCE: 440 Arg Gln Lys Thr 1 <210> SEQ ID NO 441 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 5)..(7) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 441 Arg Xaa Glu Thr Xaa Trp Xaa 1 5 <210> SEQ ID NO 442 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 5)..(7) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 442 Arg Xaa Glu Thr Xaa Trp Xaa 1 5 <210> SEQ ID NO 443 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 443 Arg Gly Asp Gly Xaa 1 5 <210> SEQ ID NO 444 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 444 Cys Arg Gly Asp Gly Xaa Cys 1 5 <210> SEQ ID NO 445 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3, 4, 8, 9, 10, 11, 12, 13)..(14) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 445 Cys Xaa Xaa Xaa Arg Leu Asp Xaa Xaa Xaa Xaa Xaa Xaa Xaa Cys 1 5 10 15 <210> SEQ ID NO 446 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 446 Cys Ala Arg Arg Leu Asp Ala Pro Cys 1 5 <210> SEQ ID NO 447 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 447 Cys Pro Ser Arg Leu Asp Ser Pro Cys 1 5 <210> SEQ ID NO 448 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 2, 3, 7, 8)..(9) <223> OTHER INFORMATION: Xaa are capable of forming a cyclizing bond <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(5) <223> OTHER INFORMATION: Feature at 1, 5 is an amino acid capable of forming a cyclying bond and attached to 1-5 amino acid linker <400> SEQUENCE: 448 Xaa Xaa Xaa Arg Gly Asp Xaa Xaa Xaa 1 5 <210> SEQ ID NO 449 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(8) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 449 Cys Xaa Cys Arg Gly Asp Cys Xaa Cys 1 5 <210> SEQ ID NO 450 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 450 Cys Asp Cys Arg Gly Asp Cys Phe Cys 1 5 <210> SEQ ID NO 451 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 451 Cys Asp Cys Arg Gly Asp Cys Leu Cys 1 5 <210> SEQ ID NO 452 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 452 Cys Leu Cys Arg Gly Asp Cys Ile Cys 1 5 <210> SEQ ID NO 453 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 2, 5, 6, 7)..(8) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 453 Xaa Xaa Asp Asp Xaa Xaa Xaa Xaa 1 5 <210> SEQ ID NO 454 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 2, 3, 6, 7, 8, 9)..(10) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 454 Xaa Xaa Xaa Asp Asp Xaa Xaa Xaa Xaa Xaa 1 5 10 <210> SEQ ID NO 455 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 455 Cys Trp Asp Asp Gly Trp Leu Cys 1 5 <210> SEQ ID NO 456 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 456 Cys Trp Asp Asp Leu Trp Trp Leu Cys 1 5 <210> SEQ ID NO 457 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 457 Cys Trp Asp Asp Gly Leu Met Cys 1 5 <210> SEQ ID NO 458 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 458 Cys Trp Asp Asp Gly Trp Met Cys 1 5 <210> SEQ ID NO 459 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 459 Cys Ser Trp Asp Asp Gly Trp Leu Cys 1 5 <210> SEQ ID NO 460 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 460 Cys Pro Asp Asp Leu Trp Trp Leu Cys 1 5 <210> SEQ ID NO 461 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(8) <223> OTHER INFORMATION: Xaa can be any of the 20 L-amino acids <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Xaa can be C, A, a-amino-y-bromobutyric acid or Hoc <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Xaa can be R, H, L or W <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Xaa can be M, F or I; Xaa <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Xaa can be D, E, I, L or V <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (12)..(12) <223> OTHER INFORMATION: Xaa can be C, A, a-amino-y-bromobutyric acid or Hoc; provided that Xaa (Pos3 or 12) is C or Hoc. <400> SEQUENCE: 461 Tyr Xaa Xaa Xaa Xaa Gly Pro Xaa Thr Trp Xaa Xaa 1 5 10 <210> SEQ ID NO 462 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 462 Cys Gln Asn Arg Tyr Thr Asp Leu Val Ala Ile Gln Asn Lys Asn Glu 1 5 10 15 <210> SEQ ID NO 463 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 463 Ala Glu Asn Trp Ala Asp Asn Glu Pro Asn Asn Lys Arg Asn Asn Glu 1 5 10 15 Asp <210> SEQ ID NO 464 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 464 Arg Lys Asn Asn Lys Thr Trp Thr Trp Val Gly Thr Lys Lys Ala Leu 1 5 10 15 Thr Asn Glu <210> SEQ ID NO 465 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <400> SEQUENCE: 465 Lys Lys Ala Leu Thr Asn Glu Ala Glu Asn Trp Ala Asp 1 5 10 <210> SEQ ID NO 466 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(15) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 466 Cys Gln Xaa Arg Tyr Thr Asp Leu Val Ala Ile Gln Asn Lys Xaa Glu 1 5 10 15 <210> SEQ ID NO 467 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3, 5, 6, 13)..(15) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 467 Arg Lys Xaa Asn Xaa Xaa Trp Thr Trp Val Gly Thr Xaa Lys Xaa Leu 1 5 10 15 Thr Glu Glu <210> SEQ ID NO 468 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (13)..(15) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 468 Ala Glu Asn Trp Ala Asp Gly Glu Pro Asn Asn Lys Xaa Asn Xaa Glu 1 5 10 15 Asp <210> SEQ ID NO 469 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3, 4, 7)..(15) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 469 Cys Xaa Xaa Xaa Tyr Thr Xaa Leu Val Ala Ile Gln Asn Lys Xaa Glu 1 5 10 15 <210> SEQ ID NO 470 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3, 4, 5, 6, 8, 13, 15)..(18) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 470 Arg Lys Xaa Xaa Xaa Xaa Trp Xaa Trp Val Gly Thr Xaa Lys Xaa Leu 1 5 10 15 Thr Xaa Glu <210> SEQ ID NO 471 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 5, 6, 7, 12, 13)..(14) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 471 Ala Xaa Asn Trp Xaa Xaa Xaa Glu Pro Asn Asn Xaa Xaa Xaa Glu Asp 1 5 10 15 <210> SEQ ID NO 472 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SELECTIN ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 3, 6, 9, 12)..(13) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 472 Xaa Lys Xaa Lys Thr Xaa Glu Ala Xaa Asn Trp Xaa Xaa 1 5 10 <210> SEQ ID NO 473 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Xaa is Asp-Arg-Met-Pro-Cys, Arg-Met-Pro-Cys, Met-Pro-Cys, Pro-Cys or Cys <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Xaa is Arg or Lys <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Xaa is Ser or Thr <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (12)..(12) <223> OTHER INFORMATION: Xaa is Cys-Lys or Cys <400> SEQUENCE: 473 Xaa Xaa Asn Phe Phe Trp Lys Thr Phe Xaa Ser Xaa 1 5 10 <210> SEQ ID NO 474 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 474 Asp Arg Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 1 5 10 15 Lys <210> SEQ ID NO 475 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 475 Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 1 5 10 15 <210> SEQ ID NO 476 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 476 Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 1 5 10 <210> SEQ ID NO 477 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 477 Asp Arg Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 1 5 10 15 <210> SEQ ID NO 478 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 478 Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 1 5 10 <210> SEQ ID NO 479 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 479 Cys Arg Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 1 5 10 <210> SEQ ID NO 480<211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 480 Asp Arg Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 1 5 10 15 <210> SEQ ID NO 481<211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 481 Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 1 5 10 15 <210> SEQ ID NO 482 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 482 Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys Lys 1 5 10 <210> SEQ ID NO 483 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 483 Asp Arg Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 1 5 10 15 <210> SEQ ID NO 484 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 484 Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 1 5 10 <210> SEQ ID NO 485 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 485 Cys Lys Asn Phe Phe Trp Lys Thr Phe Ser Ser Cys 1 5 10 <210> SEQ ID NO 486 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 486 Asp Arg Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 1 5 10 15 Lys <210> SEQ ID NO 487 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 487 Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 1 5 10 15 <210> SEQ ID NO 488 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 488 Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 1 5 10 <210> SEQ ID NO 489 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 489 Asp Arg Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 1 5 10 15 <210> SEQ ID NO 490 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 490 Met Pro Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 1 5 10 <210> SEQ ID NO 491 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 491 Cys Arg Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 1 5 10 <210> SEQ ID NO 492 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 492 Asp Arg Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 1 5 10 15 Lys <210> SEQ ID NO 493 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 493 Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 1 5 10 15 <210> SEQ ID NO 494 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 494 Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys Lys 1 5 10 <210> SEQ ID NO 495 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 495 Asp Arg Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 1 5 10 15 <210> SEQ ID NO 496 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 496 Met Pro Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 1 5 10 <210> SEQ ID NO 497 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SOMATOSTATIN OR CORTISTATIN MIMETIC PEPTIDE <400> SEQUENCE: 497 Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys 1 5 10 <210> SEQ ID NO 498 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CAP37 MIMETIC/LPS BINDING <400> SEQUENCE: 498 Asn Gln Gly Arg His Phe Cys Gly Gly Ala Leu Ile His Ala Arg Phe 1 5 10 15 Val Met Thr Ala Ala Ser Cys Phe Gln 20 25 <210> SEQ ID NO 499 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CAP37 MIMETIC/LPS BINDING <400> SEQUENCE: 499 Arg His Phe Cys Gly Gly Ala Leu Ile His Ala Arg Phe Val Met Thr 1 5 10 15 Ala Ala Ser Cys 20 <210> SEQ ID NO 500<211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CAP37 MIMETIC/LPS BINDING <400> SEQUENCE: 500 Gly Thr Arg Cys Gln Val Ala Gly Trp Gly Ser Gln Arg Ser Gly Gly 1 5 10 15 Arg Leu Ser Arg Phe Pro Arg Phe Val Asn Val 20 25 <210> SEQ ID NO 501 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF- ANTAGONIST <400> SEQUENCE: 501 Gly Glu Arg Trp Cys Phe Asp Gly Pro Arg Ala Trp Val Cys Gly Trp 1 5 10 15 Glu Ile <210> SEQ ID NO 502 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF- ANTAGONIST <400> SEQUENCE: 502 Glu Glu Leu Trp Cys Phe Asp Gly Pro Arg Ala Trp Val Cys Gly Tyr 1 5 10 15 Val Lys <210> SEQ ID NO 503 <211> LENGTH: 33 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 503 Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro Leu Phe Lys 1 5 10 15 Thr Leu Leu Ser Ala Val Gly Ser Ala Leu Ser Ser Ser Gly Gly Gln 20 25 30 Gln <210> SEQ ID NO 504 <211> LENGTH: 33 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7, 18,)..(19) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 504 Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro Leu Phe Lys 1 5 10 15 Thr Leu Leu Ser Ala Val Gly Ser Ala Leu Ser Ser Ser Gly Gly Gln 20 25 30 Glu <210> SEQ ID NO 505 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18)..(19) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 505 Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro Leu Phe Lys 1 5 10 15 Thr Leu Leu Ser Ala Val 20 <210> SEQ ID NO 506 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7, 18)..(19) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 506 Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro Leu Phe Lys 1 5 10 15 Thr Leu Leu Ser Ala Val 20 <210> SEQ ID NO 507 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8, 19)..(20) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 507 Lys Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro Leu Phe 1 5 10 15 Lys Thr Leu Leu Ser Ala Val 20 <210> SEQ ID NO 508 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9, 20)..(21) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 508 Lys Lys Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro Leu 1 5 10 15 Phe Lys Thr Leu Leu Ser Ala Val 20 <210> SEQ ID NO 509 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9, 20)..(21) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 509 Lys Lys Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro Leu 1 5 10 15 Phe Lys Thr Leu Leu Ser Ala Val 20 <210> SEQ ID NO 510 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Position 7, D amino acid residue<400> SEQUENCE: 510 Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser 1 5 10 <210> SEQ ID NO 511 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 511 Gly Ile Gly Ala Val Leu Lys Val Leu Thr Thr Gly Leu Pro Ala Leu 1 5 10 15 Ile Ser Trp Ile Lys Arg Lys Arg Gln Gln 20 25 <210> SEQ ID NO 512 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5, 8, 17)..(23) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 512 Gly Ile Gly Ala Val Leu Lys Val Leu Thr Thr Gly Leu Pro Ala Leu 1 5 10 15 Ile Ser Trp Ile Lys Arg Lys Arg Gln Gln 20 25 <210> SEQ ID NO 513 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5, 18, 17)..(23) <223> OTHER INFORMATION: Positions residues <400> SEQUENCE: 513 Gly Ile Gly Ala Val Leu Lys Val Leu Thr Thr Gly Leu Pro Ala Leu 1 5 10 15 Ile Ser Trp Ile Lys Arg Lys Arg Gln Gln 20 25 <210> SEQ ID NO 514 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5, 8, 17)..(21) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 514 Gly Ile Gly Ala Val Leu Lys Val Leu Thr Thr Gly Leu Pro Ala Leu 1 5 10 15 Ile Ser Trp Ile Lys Arg 20 <210> SEQ ID NO 515 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 5, 14)..(18) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 515 Ala Val Leu Lys Val Leu Thr Thr Gly Leu Pro Ala Leu Ile Ser Trp 1 5 10 15 Ile Lys Arg <210> SEQ ID NO 516 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3, 4, 8)..(10) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 516 Lys Leu Leu Leu Leu Leu Lys Leu Leu Leu Leu Lys 1 5 10 <210> SEQ ID NO 517 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3, 4, 8)..(10) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 517 Lys Leu Leu Leu Lys Leu Leu Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 518 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3, 4, 8)..(10) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 518 Lys Leu Leu Leu Lys Leu Lys Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 519 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 519 Lys Lys Leu Leu Lys Leu Lys Leu Lys Leu Lys Lys 1 5 10 <210> SEQ ID NO 520 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 520 Lys Leu Leu Leu Lys Leu Leu Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 521 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 521 Lys Leu Leu Leu Lys Leu Lys Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 522 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 522 Lys Leu Leu Leu Leu Lys 1 5 <210> SEQ ID NO 523 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 523 Lys Leu Leu Leu Lys Leu Leu Lys 1 5 <210> SEQ ID NO 524 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 524 Lys Leu Leu Leu Lys Leu Lys Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 525 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 525 Lys Leu Leu Leu Lys Leu Lys Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 526 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 526 Lys Leu Leu Leu Lys Leu Lys Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 527 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 527 Lys Ala Ala Ala Lys Ala Ala Ala Lys Ala Ala Lys 1 5 10 <210> SEQ ID NO 528 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 528 Lys Val Val Val Lys Val Val Val Lys Val Val Lys 1 5 10 <210> SEQ ID NO 529 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 529 Lys Val Val Val Lys Val Lys Val Lys Val Val Lys 1 5 10 <210> SEQ ID NO 530 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 530 Lys Val Val Val Lys Val Lys Val Lys Val Lys 1 5 10 <210> SEQ ID NO 531 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 531 Lys Val Val Val Lys Val Lys Val Lys Val Val Lys 1 5 10 <210> SEQ ID NO 532 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 532 Lys Leu Ile Leu Lys Leu 1 5 <210> SEQ ID NO 533 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 533 Lys Val Leu His Leu Leu 1 5 <210> SEQ ID NO 534 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 534 Leu Lys Leu Arg Leu Leu 1 5 <210> SEQ ID NO 535 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 535 Lys Pro Leu His Leu Leu 1 5 <210> SEQ ID NO 536 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 536 Lys Leu Ile Leu Lys Leu Val Arg 1 5 <210> SEQ ID NO 537 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 537 Lys Val Phe His Leu Leu His Leu 1 5 <210> SEQ ID NO 538 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 538 His Lys Phe Arg Ile Leu Lys Leu 1 5 <210> SEQ ID NO 539 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 539 Lys Pro Phe His Ile Leu His Leu 1 5 <210> SEQ ID NO 540<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 540 Lys Ile Ile Ile Lys Ile Lys Ile Lys Ile Ile Lys 1 5 10 <210> SEQ ID NO 541<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 541 Lys Ile Ile Ile Lys Ile Lys Ile Lys Ile Ile Lys 1 5 10 <210> SEQ ID NO 542 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 542 Lys Ile Ile Ile Lys Ile Lys Ile Lys Ile Ile Lys 1 5 10 <210> SEQ ID NO 543 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 543 Lys Ile Pro Ile Lys Ile Lys Ile Lys Ile Pro Lys 1 5 10 <210> SEQ ID NO 544 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 544 Lys Ile Pro Ile Lys Ile Lys Ile Lys Ile Val Lys 1 5 10 <210> SEQ ID NO 545 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 545 Arg Ile Ile Ile Arg Ile Arg Ile Arg Ile Ile Arg 1 5 10 <210> SEQ ID NO 546 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 546 Arg Ile Ile Ile Arg Ile Arg Ile Arg Ile Ile Arg 1 5 10 <210> SEQ ID NO 547 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 547 Arg Ile Ile Ile Arg Ile Arg Ile Arg Ile Ile Arg 1 5 10 <210> SEQ ID NO 548 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 548 Arg Ile Val Ile Arg Ile Arg Ile Arg Leu Ile Arg 1 5 10 <210> SEQ ID NO 549 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 549 Arg Ile Ile Val Arg Ile Arg Leu Arg Ile Ile Arg 1 5 10 <210> SEQ ID NO 550 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 550 Arg Ile Gly Ile Arg Leu Arg Val Arg Ile Ile Arg 1 5 10 <210> SEQ ID NO 551 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 551 Lys Ile Val Ile Arg Ile Arg Ile Arg Leu Ile Arg 1 5 10 <210> SEQ ID NO 552 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 552 Arg Ile Ala Val Lys Trp Arg Leu Arg Phe Ile Lys 1 5 10 <210> SEQ ID NO 553 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 553 Lys Ile Gly Trp Lys Leu Arg Val Arg Ile Ile Arg 1 5 10 <210> SEQ ID NO 554 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 554 Lys Lys Ile Gly Trp Leu Ile Ile Arg Val Arg Arg 1 5 10 <210> SEQ ID NO 555 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 555 Arg Ile Val Ile Arg Ile Arg Ile Arg Leu Ile Arg Ile Arg 1 5 10 <210> SEQ ID NO 556 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 556 Arg Ile Ile Val Arg Ile Arg Leu Arg Ile Ile Arg Val Arg 1 5 10 <210> SEQ ID NO 557 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 557 Arg Ile Gly Ile Arg Leu Arg Val Arg Ile Ile Arg Arg Val 1 5 10 <210> SEQ ID NO 558 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 558 Lys Ile Val Ile Arg Ile Arg Ala Arg Leu Ile Arg Ile Arg Ile Arg 1 5 10 15 <210> SEQ ID NO 559 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 559 Arg Ile Ile Val Lys Ile Arg Leu Arg Ile Ile Lys Lys Ile Arg Leu 1 5 10 15 <210> SEQ ID NO 560 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 560 Lys Ile Gly Ile Lys Ala Arg Val Arg Ile Ile Arg Val Lys Ile Ile 1 5 10 15 <210> SEQ ID NO 561 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 561 Arg Ile Ile Val His Ile Arg Leu Arg Ile Ile His His Ile Arg Leu 1 5 10 15 <210> SEQ ID NO 562 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 562 His Ile Gly Ile Lys Ala His Val Arg Ile Ile Arg Val His Ile Ile 1 5 10 15 <210> SEQ ID NO 563 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 563 Arg Ile Tyr Val Lys Ile His Leu Arg Tyr Ile Lys Lys Ile Arg Leu 1 5 10 15 <210> SEQ ID NO 564 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 564 Lys Ile Gly His Lys Ala Arg Val His Ile Ile Arg Tyr Lys Ile Ile 1 5 10 15 <210> SEQ ID NO 565 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 565 Arg Ile Tyr Val Lys Pro His Pro Arg Tyr Ile Lys Lys Ile Arg Leu 1 5 10 15 <210> SEQ ID NO 566 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 566 Lys Pro Gly His Lys Ala Arg Pro His Ile Ile Arg Tyr Lys Ile Ile 1 5 10 15 <210> SEQ ID NO 567 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 567 Lys Ile Val Ile Arg Ile Arg Ile Arg Leu Ile Arg Ile Arg Ile Arg 1 5 10 15 Lys Ile Val <210> SEQ ID NO 568 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 568 Arg Ile Ile Val Lys Ile Arg Leu Arg Ile Ile Lys Lys Ile Arg Leu 1 5 10 15 Ile Lys Lys <210> SEQ ID NO 569 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 569 Lys Ile Gly Trp Lys Leu Arg Val Arg Ile Ile Arg Val Lys Ile Gly 1 5 10 15 Arg Leu Arg <210> SEQ ID NO 570 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 570 Lys Ile Val Ile Arg Ile Arg Ile Arg Leu Ile Arg Ile Arg Ile Arg 1 5 10 15 Lys Ile Val Lys Val Lys Arg Ile Arg 20 25 <210> SEQ ID NO 571 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 571 Arg Phe Ala Val Lys Ile Arg Leu Arg Ile Ile Lys Lys Ile Arg Leu 1 5 10 15 Ile Lys Lys Ile Arg Lys Arg Val Ile Lys 20 25 <210> SEQ ID NO 572 <211> LENGTH: 30 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 572 Lys Ala Gly Trp Lys Leu Arg Val Arg Ile Ile Arg Val Lys Ile Gly 1 5 10 15 Arg Leu Arg Lys Ile Gly Trp Lys Lys Arg Val Arg Ile Lys 20 25 30 <210> SEQ ID NO 573 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 573 Arg Ile Tyr Val Lys Pro His Pro Arg Tyr Ile Lys Lys Ile Arg Leu 1 5 10 15 <210> SEQ ID NO 574 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 574 Lys Pro Gly His Lys Ala Arg Pro His Ile Ile Arg Tyr Lys Ile Ile 1 5 10 15 <210> SEQ ID NO 575 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 575 Lys Ile Val Ile Arg Ile Arg Ile Arg Leu Ile Arg Ile Arg Ile Arg 1 5 10 15 Lys Ile Val <210> SEQ ID NO 576 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 576 Arg Ile Ile Val Lys Ile Arg Leu Arg Ile Ile Lys Lys Ile Arg Leu 1 5 10 15 Ile Lys Lys <210> SEQ ID NO 577 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 577 Arg Ile Tyr Val Ser Lys Ile Ser Ile Tyr Ile Lys Lys Ile Arg Leu 1 5 10 15 <210> SEQ ID NO 578 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 578 Lys Ile Val Ile Phe Thr Arg Ile Arg Leu Thr Ser Ile Arg Ile Arg 1 5 10 15 Ser Ile Val <210> SEQ ID NO 579 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 579 Lys Pro Ile His Lys Ala Arg Pro Thr Ile Ile Arg Tyr Lys Met Ile 1 5 10 15 <210> SEQ ID NO 580 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, disulfide bond to position 26<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (26)..(26) <223> OTHER INFORMATION: Position 26, disulfide bond to position 1 <400> SEQUENCE: 580 Xaa Cys Lys Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro 1 5 10 15 Leu Phe Lys Thr Leu Leu Ser Ala Val Cys 20 25 <210> SEQ ID NO 581 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 581 Cys Lys Lys Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser Pro 1 5 10 15 Leu Phe Lys Thr Leu Leu Ser Ala Val Cys 20 25 <210> SEQ ID NO 582 <211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 582 Cys Lys Lys Lys Gly Phe Phe Ala Leu Ile Pro Lys Ile Ile Ser Ser 1 5 10 15 Pro Leu Phe Lys Thr Leu Leu Ser Ala Val Cys 20 25 <210> SEQ ID NO 583 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, disulfide bond toposition 17<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (17)..(17) <223> OTHER INFORMATION: Position 17, disulfide bond toposition 1<400> SEQUENCE: 583 Xaa Cys Arg Ile Val Ile Arg Ile Arg Ile Arg Leu Ile Arg Ile Arg 1 5 10 15 Cys <210> SEQ ID NO 584 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, disulfide bond to position 19<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (19)..(19) <223> OTHER INFORMATION: Position 19, disulfide bond to position 1<400> SEQUENCE: 584 Xaa Cys Lys Pro Gly His Lys Ala Arg Pro His Ile Ile Arg Tyr Lys 1 5 10 15 Ile Ile Cys <210> SEQ ID NO 585 <211> LENGTH: 29 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, disulfide bond to position 29<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (29)..(29) <223> OTHER INFORMATION: Position 29, disulfide bond to position 1<400> SEQUENCE: 585 Xaa Cys Arg Phe Ala Val Lys Ile Arg Leu Arg Ile Ile Lys Lys Ile 1 5 10 15 Arg Leu Ile Lys Lys Ile Arg Lys Arg Val Ile Lys Cys 20 25 <210> SEQ ID NO 586 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 586 Lys Leu Leu Leu Lys Leu Leu Leu Lys Leu Leu Lys Cys 1 5 10 <210> SEQ ID NO 587 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 587 Lys Leu Leu Leu Lys Leu Leu Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 588 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 588 Lys Leu Leu Leu Lys Leu Lys Leu Lys Leu Leu Lys Cys 1 5 10 <210> SEQ ID NO 589 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: ANTIPATHOGENIC PEPTIDE <400> SEQUENCE: 589 Lys Leu Leu Leu Lys Leu Leu Leu Lys Leu Leu Lys 1 5 10 <210> SEQ ID NO 590 <211> LENGTH: 28 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 590 His Ser Asp Ala Val Phe Tyr Asp Asn Tyr Thr Arg Leu Arg Lys Gln 1 5 10 15 Met Ala Val Lys Lys Tyr Leu Asn Ser Ile Leu Asn 20 25 <210> SEQ ID NO 591 <211> LENGTH: 28 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 591 His Ser Asp Ala Val Phe Tyr Asp Asn Tyr Thr Arg Leu Arg Lys Gln 1 5 10 15 Met Ala Val Lys Lys Tyr Leu Asn Ser Ile Leu Asn 20 25 <210> SEQ ID NO 592 <211> LENGTH: 3 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is L-Lys, D-Lys or anornithinyl residue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Position 2, Xaa is L-Tyr, D-Tyr, Phe, Trp or ap-aminophenylalanyl residue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3 is a hydrophobic aliphatic aminoacid residue, Position 3, optional attachment to Leu, norleucyl,D-Ala, Asn-Ser, Asn-Ser-Ile-, Asn-Ser-Tyr, Ser-Ile-Leu, Asn-Ser-Tyr-Leu or Asn-Ser-Tyr-Leu-Asn <400> SEQUENCE: 592 Xaa Xaa Xaa 1 <210> SEQ ID NO 593 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(3) <223> OTHER INFORMATION: Position 1, Xaa is either absent, a hydrophobicaliphatic residue (X5), X5-Asn, Tyr-X5, Lys-X5, Lys-X5-Asn, Lys-Tyr-X5, Lys-Tyr-X5-Asn, Lys-Lys-Tyr-X5, Lys-Lys-Tyr-X5-Asn, Val-Lys-Lys-Tyr-X5, Val-Ala-Lys-Lys-Tyr-X5-Asn, or Ala-Val-Lys-Lys-Tyr-X5-Asn <400> SEQUENCE: 593 Xaa Ser Xaa Leu Asn 1 5 <210> SEQ ID NO 594 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 5, 6)..(7) <223> OTHER INFORMATION: Positions acid residues as defined in WO97/40070 <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is a hydrophobic aliphaticaminod acid residue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Position 7, is a covalent bond or Asn, Ser,Ile, Tyr, Leu, Asn-Ser, Asn-Ser-Ile, Asn-Ser-Tyr, Asn-Ser-Ile-Leu, Asn-Ser-Tyr-Leu, Asn-Ser-Ile-Leu-Asn or Asn-Ser-Tyr-Leu-Asn. <400> SEQUENCE: 594 Xaa Lys Lys Tyr Xaa Xaa Xaa 1 5 <210> SEQ ID NO 595 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 595 Lys Lys Tyr Leu 1 <210> SEQ ID NO 596 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 596 Asn Ser Ile Leu Asn 1 5 <210> SEQ ID NO 597 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 597 Lys Lys Tyr Leu 1 <210> SEQ ID NO 598 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 598 Lys Lys Tyr Ala 1 <210> SEQ ID NO 599 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 599 Ala Val Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 600<211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 600 Ser Ile Leu Asn 1 <210> SEQ ID NO 601<211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 601 Lys Lys Tyr Val 1 <210> SEQ ID NO 602 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa is a lauric acid residue<400> SEQUENCE: 602 Ser Ile Xaa Asn 1 <210> SEQ ID NO 603 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is a norleucyl residue<400> SEQUENCE: 603 Lys Lys Tyr Leu Xaa 1 5 <210> SEQ ID NO 604 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 604 Asn Ser Tyr Leu Asn 1 5 <210> SEQ ID NO 605 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 605 Asn Ser Ile Tyr Asn 1 5 <210> SEQ ID NO 606 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 606 Lys Lys Tyr Leu Pro Pro Asn Ser Ile Leu Asn 1 5 10 <210> SEQ ID NO 607 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a lauric acid residue<400> SEQUENCE: 607 Xaa Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 608 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a caproic acid residue<400> SEQUENCE: 608 Xaa Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 609 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is a norleucyl residue<400> SEQUENCE: 609 Lys Lys Tyr Xaa 1 <210> SEQ ID NO 610 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 610 Val Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 611 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 611 Leu Asn Ser Ile Leu Asn 1 5 <210> SEQ ID NO 612 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 612 Tyr Leu Asn Ser Ile Leu Asn 1 5 <210> SEQ ID NO 613 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 613 Lys Lys Tyr Leu Asn 1 5 <210> SEQ ID NO 614 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 614 Lys Lys Tyr Leu Asn Ser 1 5 <210> SEQ ID NO 615 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 615 Lys Lys Tyr Leu Asn Ser Ile 1 5 <210> SEQ ID NO 616 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 616 Lys Lys Tyr Leu Asn Ser Ile Leu 1 5 <210> SEQ ID NO 617 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 617 Lys Lys Tyr Leu 1 <210> SEQ ID NO 618 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 618 Lys Lys Tyr Asp Ala 1 5 <210> SEQ ID NO 619 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 619 Ala Val Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 620 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 620 Asn Ser Ile Leu Asn 1 5 <210> SEQ ID NO 621 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 621 Lys Lys Tyr Val 1 <210> SEQ ID NO 622 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(3) <223> OTHER INFORMATION: Position 3, Xaa is a lauric acid residue<400> SEQUENCE: 622 Xaa Ile Xaa Asn 1 <210> SEQ ID NO 623 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 623 Asn Ser Tyr Leu Asn 1 5 <210> SEQ ID NO 624 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 624 Asn Ser Ile Tyr Asn 1 5 <210> SEQ ID NO 625 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is a norleucyl residue<400> SEQUENCE: 625 Lys Lys Tyr Leu Xaa 1 5 <210> SEQ ID NO 626 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 626 Lys Lys Tyr Leu Pro Pro Asn Ser Ile Leu Asn 1 5 10 <210> SEQ ID NO 627 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 627 Lys Lys Tyr Leu 1 <210> SEQ ID NO 628 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 628 Lys Lys Tyr Asp Ala 1 5 <210> SEQ ID NO 629 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 629 Ala Val Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 630 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 630 Asn Ser Ile Leu Asn 1 5 <210> SEQ ID NO 631 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 631 Lys Lys Tyr Val 1 <210> SEQ ID NO 632 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(3) <223> OTHER INFORMATION: Position 3, Xaa is a lauric acid residue<400> SEQUENCE: 632 Xaa Ile Xaa Asn 1 <210> SEQ ID NO 633 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a lauric acid residue<400> SEQUENCE: 633 Xaa Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 634 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a caproic acid residue<400> SEQUENCE: 634 Xaa Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 635 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is a norleucyl residue<400> SEQUENCE: 635 Lys Lys Tyr Xaa 1 <210> SEQ ID NO 636 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 636 Val Lys Lys Tyr Leu 1 5 <210> SEQ ID NO 637 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 637 Leu Asn Ser Ile Leu Asn 1 5 <210> SEQ ID NO 638 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 638 Tyr Leu Asn Ser Ile Leu Asn 1 5 <210> SEQ ID NO 639 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is a norleucyl residue<400> SEQUENCE: 639 Lys Lys Tyr Leu Xaa 1 5 <210> SEQ ID NO 640 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 640 Lys Lys Tyr Leu Asn 1 5 <210> SEQ ID NO 641 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 641 Lys Lys Tyr Leu Asn Ser 1 5 <210> SEQ ID NO 642 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 642 Lys Lys Tyr Leu Asn Ser Ile 1 5 <210> SEQ ID NO 643 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 643 Lys Lys Tyr Leu Asn Ser Ile Leu 1 5 <210> SEQ ID NO 644 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 644 Lys Lys Lys Tyr Leu Asp 1 5 <210> SEQ ID NO 645 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Positions <400> SEQUENCE: 645 Xaa Cys Lys Lys Tyr Leu Cys 1 5 <210> SEQ ID NO 646 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Positions <400> SEQUENCE: 646 Cys Lys Lys Tyr Leu Lys 1 5 <210> SEQ ID NO 647 <211> LENGTH: 4 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Position 4, D amino acid residue<400> SEQUENCE: 647 Lys Lys Tyr Ala 1 <210> SEQ ID NO 648 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 648 Trp Trp Thr Asp Thr Gly Leu Trp 1 5 <210> SEQ ID NO 649 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 649 Trp Trp Thr Asp Asp Gly Leu Trp 1 5 <210> SEQ ID NO 650 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 650 Trp Trp Asp Thr Arg Gly Leu Trp Val Trp Thr Ile 1 5 10 <210> SEQ ID NO 651 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 651 Phe Trp Gly Asn Asp Gly Ile Trp Leu Glu Ser Gly 1 5 10 <210> SEQ ID NO 652 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 652 Asp Trp Asp Gln Phe Gly Leu Trp Arg Gly Ala Ala 1 5 10 <210> SEQ ID NO 653 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 653 Arg Trp Asp Asp Asn Gly Leu Trp Val Val Val Leu 1 5 10 <210> SEQ ID NO 654 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 654 Ser Gly Met Trp Ser His Tyr Gly Ile Trp Met Gly 1 5 10 <210> SEQ ID NO 655 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 655 Gly Gly Arg Trp Asp Gln Ala Gly Leu Trp Val Ala 1 5 10 <210> SEQ ID NO 656 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 656 Lys Leu Trp Ser Glu Gln Gly Ile Trp Met Gly Glu 1 5 10 <210> SEQ ID NO 657 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 657 Cys Trp Ser Met His Gly Leu Trp Leu Cys 1 5 10 <210> SEQ ID NO 658 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 658 Gly Cys Trp Asp Asn Thr Gly Ile Trp Val Pro Cys 1 5 10 <210> SEQ ID NO 659 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 659 Asp Trp Asp Thr Arg Gly Leu Trp Val Tyr 1 5 10 <210> SEQ ID NO 660<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 660 Ser Leu Trp Asp Glu Asn Gly Ala Trp Ile 1 5 10 <210> SEQ ID NO 661<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 661 Lys Trp Asp Asp Arg Gly Leu Trp Met His 1 5 10 <210> SEQ ID NO 662 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 662 Gln Ala Trp Asn Glu Arg Gly Leu Trp Thr 1 5 10 <210> SEQ ID NO 663 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 663 Gln Trp Asp Thr Arg Gly Leu Trp Val Ala 1 5 10 <210> SEQ ID NO 664 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 664 Trp Asn Val His Gly Ile Trp Gln Glu 1 5 <210> SEQ ID NO 665 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 665 Ser Trp Asp Thr Arg Gly Leu Trp Val Glu 1 5 10 <210> SEQ ID NO 666 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 666 Asp Trp Asp Thr Arg Gly Leu Trp Val Ala 1 5 10 <210> SEQ ID NO 667 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 667 Ser Trp Gly Arg Asp Gly Leu Trp Ile Glu 1 5 10 <210> SEQ ID NO 668 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 668 Glu Trp Thr Asp Asn Gly Leu Trp Ala Leu 1 5 10 <210> SEQ ID NO 669 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 669 Ser Trp Asp Glu Lys Gly Leu Trp Ser Ala 1 5 10 <210> SEQ ID NO 670 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VIP-MIMETIC PEPTIDE <400> SEQUENCE: 670 Ser Trp Asp Ser Ser Gly Leu Trp Met Asp 1 5 10 <210> SEQ ID NO 671 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 671 Ser His Leu Tyr Trp Gln Pro Tyr Ser Val Gln 1 5 10 <210> SEQ ID NO 672 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 672 Thr Leu Val Tyr Trp Gln Pro Tyr Ser Leu Gln Thr 1 5 10 <210> SEQ ID NO 673 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 673 Arg Gly Asp Tyr Trp Gln Pro Tyr Ser Val Gln Ser 1 5 10 <210> SEQ ID NO 674 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 674 Val His Val Tyr Trp Gln Pro Tyr Ser Val Gln Thr 1 5 10 <210> SEQ ID NO 675 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 675 Arg Leu Val Tyr Trp Gln Pro Tyr Ser Val Gln Thr 1 5 10 <210> SEQ ID NO 676 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 676 Ser Arg Val Trp Phe Gln Pro Tyr Ser Leu Gln Ser 1 5 10 <210> SEQ ID NO 677 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 677 Asn Met Val Tyr Trp Gln Pro Tyr Ser Ile Gln Thr 1 5 10 <210> SEQ ID NO 678 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 678 Ser Val Val Phe Trp Gln Pro Tyr Ser Val Gln Thr 1 5 10 <210> SEQ ID NO 679 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 679 Thr Phe Val Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 680 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 680 Thr Leu Val Tyr Trp Gln Pro Tyr Ser Ile Gln Arg 1 5 10 <210> SEQ ID NO 681 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 681 Arg Leu Val Tyr Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 682 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 682 Ser Pro Val Phe Trp Gln Pro Tyr Ser Ile Gln Ile 1 5 10 <210> SEQ ID NO 683 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 683 Trp Ile Glu Trp Trp Gln Pro Tyr Ser Val Gln Ser 1 5 10 <210> SEQ ID NO 684<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 684 Ser Leu Ile Tyr Trp Gln Pro Tyr Ser Leu Gln Met 1 5 10 <210> SEQ ID NO 685 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 685 Thr Arg Leu Tyr Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 686 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 686 Arg Cys Asp Tyr Trp Gln Pro Tyr Ser Val Gln Thr 1 5 10 <210> SEQ ID NO 687 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 687 Met Arg Val Phe Trp Gln Pro Tyr Ser Val Gln Asn 1 5 10 <210> SEQ ID NO 688 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 688 Lys Ile Val Tyr Trp Gln Pro Tyr Ser Val Gln Thr 1 5 10 <210> SEQ ID NO 689 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 689 Arg His Leu Tyr Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 690 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 690 Ala Leu Val Trp Trp Gln Pro Tyr Ser Glu Gln Ile 1 5 10 <210> SEQ ID NO 691 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 691 Ser Arg Val Trp Phe Gln Pro Tyr Ser Leu Gln Ser 1 5 10 <210> SEQ ID NO 692 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 692 Trp Glu Gln Pro Tyr Ala Leu Pro Leu Glu 1 5 10 <210> SEQ ID NO 693 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 693 Gln Leu Val Trp Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 694 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 694 Asp Leu Arg Tyr Trp Gln Pro Tyr Ser Val Gln Val 1 5 10 <210> SEQ ID NO 695 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 695 Glu Leu Val Trp Trp Gln Pro Tyr Ser Leu Gln Leu 1 5 10 <210> SEQ ID NO 696 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 696 Asp Leu Val Trp Trp Gln Pro Tyr Ser Val Gln Trp 1 5 10 <210> SEQ ID NO 697 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 697 Asn Gly Asn Tyr Trp Gln Pro Tyr Ser Phe Gln Val 1 5 10 <210> SEQ ID NO 698 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 698 Glu Leu Val Tyr Trp Gln Pro Tyr Ser Ile Gln Arg 1 5 10 <210> SEQ ID NO 699 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 699 Glu Leu Met Tyr Trp Gln Pro Tyr Ser Val Gln Glu 1 5 10 <210> SEQ ID NO 700 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 700 Asn Leu Leu Tyr Trp Gln Pro Tyr Ser Met Gln Asp 1 5 10 <210> SEQ ID NO 701 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 701 Gly Tyr Glu Trp Tyr Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 702 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 702 Ser Arg Val Trp Tyr Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 703 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 703 Leu Ser Glu Gln Tyr Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 704 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 704 Gly Gly Gly Trp Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 705 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 705 Val Gly Arg Trp Tyr Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 706 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 706 Val His Val Tyr Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 707 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 707 Gln Ala Arg Trp Tyr Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 708 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 708 Val His Val Tyr Trp Gln Pro Tyr Ser Val Gln Thr 1 5 10 <210> SEQ ID NO 709 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 709 Arg Ser Val Tyr Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 710 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 710 Thr Arg Val Trp Phe Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 711 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 711 Gly Arg Ile Trp Phe Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 712 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 712 Gly Arg Val Trp Phe Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 713 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 713 Ala Arg Thr Trp Tyr Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 714 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 714 Ala Arg Val Trp Trp Gln Pro Tyr Ser Val Gln Met 1 5 10 <210> SEQ ID NO 715 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 715 Arg Leu Met Phe Tyr Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 716 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 716 Glu Ser Met Trp Tyr Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 717 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 717 His Phe Gly Trp Trp Gln Pro Tyr Ser Val His Met 1 5 10 <210> SEQ ID NO 718 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 718 Ala Arg Phe Trp Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 719 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 719 Arg Leu Val Tyr Trp Gln Pro Tyr Ala Pro Ile Tyr 1 5 10 <210> SEQ ID NO 720<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 720 Arg Leu Val Tyr Trp Gln Pro Tyr Ser Tyr Gln Thr 1 5 10 <210> SEQ ID NO 721<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 721 Arg Leu Val Tyr Trp Gln Pro Tyr Ser Leu Pro Ile 1 5 10 <210> SEQ ID NO 722 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 722 Arg Leu Val Tyr Trp Gln Pro Tyr Ser Val Gln Ala 1 5 10 <210> SEQ ID NO 723 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 723 Ser Arg Val Trp Tyr Gln Pro Tyr Ala Lys Gly Leu 1 5 10 <210> SEQ ID NO 724 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 724 Ser Arg Val Trp Tyr Gln Pro Tyr Ala Gln Gly Leu 1 5 10 <210> SEQ ID NO 725 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 725 Ser Arg Val Trp Tyr Gln Pro Tyr Ala Met Pro Leu 1 5 10 <210> SEQ ID NO 726 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 726 Ser Arg Val Trp Tyr Gln Pro Tyr Ser Val Gln Ala 1 5 10 <210> SEQ ID NO 727 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 727 Ser Arg Val Trp Tyr Gln Pro Tyr Ser Leu Gly Leu 1 5 10 <210> SEQ ID NO 728 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 728 Ser Arg Val Trp Tyr Gln Pro Tyr Ala Arg Glu Leu 1 5 10 <210> SEQ ID NO 729 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 729 Ser Arg Val Trp Tyr Gln Pro Tyr Ser Arg Gln Pro 1 5 10 <210> SEQ ID NO 730 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 730 Ser Arg Val Trp Tyr Gln Pro Tyr Phe Val Gln Pro 1 5 10 <210> SEQ ID NO 731 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 731 Glu Tyr Glu Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 732 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 732 Ile Pro Glu Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 733 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 733 Ser Arg Ile Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 734 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 734 Asp Pro Leu Phe Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 735 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 735 Ser Arg Gln Trp Val Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 736 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 736 Ile Arg Ser Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 737 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 737 Arg Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 738 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 738 Arg Leu Leu Trp Val Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 739 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 739 Glu Tyr Arg Trp Phe Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 740 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 740 Asp Ala Tyr Trp Val Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 741 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 741 Trp Ser Gly Tyr Phe Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 742 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 742 Asn Ile Glu Phe Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 743 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 743 Thr Arg Asp Trp Val Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 744 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 744 Asp Ser Ser Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 745 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 745 Ile Gly Asn Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 746 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 746 Asn Leu Arg Trp Asp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 747 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 747 Leu Pro Glu Phe Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 748<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 748 Asp Ser Tyr Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 749 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 749 Arg Ser Gln Tyr Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 750 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 750 Ala Arg Phe Trp Leu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 751 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 751 Asn Ser Tyr Phe Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 752 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 752 Arg Phe Met Tyr Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 753 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 753 Ala His Leu Phe Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 754 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 754 Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 <210> SEQ ID NO 755 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 755 Tyr Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 <210> SEQ ID NO 756 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 756 Tyr Phe Gln Pro Tyr Ala Leu Gly Leu 1 5 <210> SEQ ID NO 757<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 757 Tyr Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 758 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 758 Arg Trp Trp Gln Pro Tyr Ala Thr Pro Leu 1 5 10 <210> SEQ ID NO 759 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 759 Gly Trp Tyr Gln Pro Tyr Ala Leu Gly Phe 1 5 10 <210> SEQ ID NO 760 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 760 Tyr Trp Tyr Gln Pro Tyr Ala Leu Gly Leu 1 5 10 <210> SEQ ID NO 761<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 761 Ile Trp Tyr Gln Pro Tyr Ala Met Pro Leu 1 5 10 <210> SEQ ID NO 762 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 762 Ser Asn Met Gln Pro Tyr Gln Arg Leu Ser 1 5 10 <210> SEQ ID NO 763<211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 763 Thr Phe Val Tyr Trp Gln Pro Tyr Ala Val Gly Leu Pro Ala Ala Glu 1 5 10 15 Thr Ala Cys Asn 20 <210> SEQ ID NO 764 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 764 Thr Phe Val Tyr Trp Gln Pro Tyr Ser Val Gln Met Thr Ile Thr Gly 1 5 10 15 Lys Val Thr Met 20 <210> SEQ ID NO 765 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (12, 13)..(16) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 765 Thr Phe Val Tyr Trp Gln Pro Tyr Ser Ser His Xaa Xaa Val Pro Xaa 1 5 10 15 Gly Phe Pro Leu 20 <210> SEQ ID NO 766 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 766 Thr Phe Val Tyr Trp Gln Pro Tyr Tyr Gly Asn Pro Gln Trp Ala Ile 1 5 10 15 His Val Arg His 20 <210> SEQ ID NO 767 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 767 Thr Phe Val Tyr Trp Gln Pro Tyr Val Leu Leu Glu Leu Pro Glu Gly 1 5 10 15 Ala Val Arg Ala 20 <210> SEQ ID NO 768 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 768 Thr Phe Val Tyr Trp Gln Pro Tyr Val Asp Tyr Val Trp Pro Ile Pro 1 5 10 15 Ile Ala Gln Val 20 <210> SEQ ID NO 769 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 769 Gly Trp Tyr Gln Pro Tyr Val Asp Gly Trp Arg 1 5 10 <210> SEQ ID NO 770 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 770 Arg Trp Glu Gln Pro Tyr Val Lys Asp Gly Trp Ser 1 5 10 <210> SEQ ID NO 771 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 771 Glu Trp Tyr Gln Pro Tyr Ala Leu Gly Trp Ala Arg 1 5 10 <210> SEQ ID NO 772 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 772 Gly Trp Trp Gln Pro Tyr Ala Arg Gly Leu 1 5 10 <210> SEQ ID NO 773<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 773 Leu Phe Glu Gln Pro Tyr Ala Lys Ala Leu Gly Leu 1 5 10 <210> SEQ ID NO 774 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 774 Gly Trp Glu Gln Pro Tyr Ala Arg Gly Leu Ala Gly 1 5 10 <210> SEQ ID NO 775 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 775 Ala Trp Val Gln Pro Tyr Ala Thr Pro Leu Asp Glu 1 5 10 <210> SEQ ID NO 776 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 776 Met Trp Tyr Gln Pro Tyr Ser Ser Gln Pro Ala Glu 1 5 10 <210> SEQ ID NO 777 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 777 Gly Trp Thr Gln Pro Tyr Ser Gln Gln Gly Glu Val 1 5 10 <210> SEQ ID NO 778 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 778 Asp Trp Phe Gln Pro Tyr Ser Ile Gln Ser Asp Glu 1 5 10 <210> SEQ ID NO 779 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 779 Pro Trp Ile Gln Pro Tyr Ala Arg Gly Phe Gly 1 5 10 <210> SEQ ID NO 780<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 780 Arg Pro Leu Tyr Trp Gln Pro Tyr Ser Val Gln Val 1 5 10 <210> SEQ ID NO 781<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 781 Thr Leu Ile Tyr Trp Gln Pro Tyr Ser Val Gln Ile 1 5 10 <210> SEQ ID NO 782 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 782 Arg Phe Asp Tyr Trp Gln Pro Tyr Ser Asp Gln Thr 1 5 10 <210> SEQ ID NO 783 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 783 Trp His Gln Phe Val Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 784 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 784 Glu Trp Asp Ser Val Tyr Trp Gln Pro Tyr Ser Val Gln Thr Leu Leu 1 5 10 15 Arg <210> SEQ ID NO 785 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 785 Trp Glu Gln Asn Val Tyr Trp Gln Pro Tyr Ser Val Gln Ser Phe Ala 1 5 10 15 Asp <210> SEQ ID NO 786 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 786 Ser Asp Val Val Tyr Trp Gln Pro Tyr Ser Val Gln Ser Leu Glu Met 1 5 10 15 <210> SEQ ID NO 787 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 787 Tyr Tyr Asp Gly Val Tyr Trp Gln Pro Tyr Ser Val Gln Val Met Pro 1 5 10 15 Ala <210> SEQ ID NO 788 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 788 Ser Asp Ile Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 789<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 789 Gln Arg Ile Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 790 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 790 Ser Arg Ile Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 791 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 791 Arg Ser Leu Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 792 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 792 Thr Ile Ile Trp Glu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 793 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 793 Trp Glu Thr Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 794<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 794 Ser Tyr Asp Trp Glu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 795 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 795 Ser Arg Ile Trp Cys Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 796 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 796 Glu Ile Met Phe Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 797 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 797 Asp Tyr Val Trp Gln Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 798 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 798 Met Asp Leu Leu Val Gln Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 799 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 799 Gly Ser Lys Val Ile Leu Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 800 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 800 Arg Gln Gly Ala Asn Ile Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 801 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 801 Gly Gly Gly Asp Glu Pro Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 802 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 802 Ser Gln Leu Glu Arg Thr Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 803 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 803 Glu Thr Trp Val Arg Glu Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 804 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 804 Lys Lys Gly Ser Thr Gln Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 805 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 805 Leu Gln Ala Arg Met Asn Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 806 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 806 Glu Pro Arg Ser Gln Lys Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 807<211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 807 Val Lys Gln Lys Trp Arg Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 808 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 808 Leu Arg Arg His Asp Val Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 809 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 809 Arg Ser Thr Ala Ser Ile Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 810 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 810 Glu Ser Lys Glu Asp Gln Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 811 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 811 Glu Gly Leu Thr Met Lys Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 812<211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 812 Glu Gly Ser Arg Glu Gly Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 813 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 813 Val Ile Glu Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 814 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 814 Val Trp Tyr Trp Glu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 815 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 815 Ala Ser Glu Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 816 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 816 Phe Tyr Glu Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 817 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 817 Glu Gly Trp Trp Val Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 818 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 818 Trp Gly Glu Trp Leu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 819 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 819 Asp Tyr Val Trp Glu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 820 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 820 Ala His Thr Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 821 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 821 Phe Ile Glu Trp Phe Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 822 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 822 Trp Leu Ala Trp Glu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 823 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 823 Val Met Glu Trp Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 824 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 824 Glu Arg Met Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 825 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3, 5)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 825 Asn Xaa Xaa Trp Xaa Xaa Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 826 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 826 Trp Gly Asn Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 827 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 827 Thr Leu Tyr Trp Glu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 828 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 828 Val Trp Arg Trp Glu Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 829 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 829 Leu Leu Trp Thr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 830 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 830 Ser Arg Ile Trp Xaa Xaa Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 831 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 831 Ser Asp Ile Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 832 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 832 Trp Gly Tyr Tyr Xaa Xaa Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 833 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 833 Thr Ser Gly Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 834 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 834 Val His Pro Tyr Xaa Xaa Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 835 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 835 Glu His Ser Tyr Phe Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 836 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(2) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 836 Xaa Xaa Ile Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 837 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 837 Ala Gln Leu His Ser Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 838 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 838 Trp Ala Asn Trp Phe Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 839 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 839 Ser Arg Leu Tyr Ser Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 840<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 840 Gly Val Thr Phe Ser Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 841<211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 841 Ser Ile Val Trp Ser Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 842 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 842 Ser Arg Asp Leu Val Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 843 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 843 His Trp Gly His Val Tyr Trp Gln Pro Tyr Ser Val Gln Asp Asp Leu 1 5 10 15 Gly <210> SEQ ID NO 844 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 844 Ser Trp His Ser Val Tyr Trp Gln Pro Tyr Ser Val Gln Ser Val Pro 1 5 10 15 Glu <210> SEQ ID NO 845 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 845 Trp Arg Asp Ser Val Tyr Trp Gln Pro Tyr Ser Val Gln Pro Glu Ser 1 5 10 15 Ala <210> SEQ ID NO 846 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 846 Thr Trp Asp Ala Val Tyr Trp Gln Pro Tyr Ser Val Gln Lys Trp Leu 1 5 10 15 Asp <210> SEQ ID NO 847 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 847 Thr Pro Pro Trp Val Tyr Trp Gln Pro Tyr Ser Val Gln Ser Leu Asp 1 5 10 15 Pro <210> SEQ ID NO 848 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 848 Tyr Trp Ser Ser Val Tyr Trp Gln Pro Tyr Ser Val Gln Ser Val His 1 5 10 15 Ser <210> SEQ ID NO 849 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 849 Tyr Trp Tyr Gln Pro Tyr Ala Leu Gly Leu 1 5 10 <210> SEQ ID NO 850 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 850 Tyr Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 851 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 851 Glu Trp Ile Gln Pro Tyr Ala Thr Gly Leu 1 5 10 <210> SEQ ID NO 852 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 852 Asn Trp Glu Gln Pro Tyr Ala Lys Pro Leu 1 5 10 <210> SEQ ID NO 853 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 853 Ala Phe Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 854 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 854 Phe Leu Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 855<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 855 Val Cys Lys Gln Pro Tyr Leu Glu Trp Cys 1 5 10 <210> SEQ ID NO 856 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 856 Glu Thr Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 857 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 857 Gln Gly Trp Leu Thr Trp Gln Asp Ser Val Asp Met Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 858 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 858 Phe Ser Glu Ala Gly Tyr Thr Trp Pro Glu Asn Thr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 859 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 859 Thr Glu Ser Pro Gly Gly Leu Asp Trp Ala Lys Ile Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 860 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 860 Asp Gly Tyr Asp Arg Trp Arg Gln Ser Gly Glu Arg Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 861<211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 861 Thr Ala Asn Val Ser Ser Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 862 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 862 Ser Val Gly Glu Asp His Asn Phe Trp Thr Ser Glu Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 863 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 863 Met Asn Asp Gln Thr Ser Glu Val Ser Thr Phe Pro Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 864 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 864 Ser Trp Ser Glu Ala Phe Glu Gln Pro Arg Asn Leu Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 865 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 865 Gln Tyr Ala Glu Pro Ser Ala Leu Asn Asp Trp Gly Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 866 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 866 Asn Gly Asp Trp Ala Thr Ala Asp Trp Ser Asn Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 867 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 867 Thr His Asp Glu His Ile Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 868 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 868 Met Leu Glu Lys Thr Tyr Thr Thr Trp Thr Pro Gly Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 869 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 869 Trp Ser Asp Pro Leu Thr Arg Asp Ala Asp Leu Tyr Trp Gln Pro Tyr 1 5 10 15 Ala Leu Pro Leu 20 <210> SEQ ID NO 870 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 870 Ser Asp Ala Phe Thr Thr Gln Asp Ser Gln Ala Met Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 871 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 871 Gly Asp Asp Ala Ala Trp Arg Thr Asp Ser Leu Thr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 872 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 872 Ala Ile Ile Arg Gln Leu Tyr Arg Trp Ser Glu Met Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 873 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 873 Glu Asn Thr Tyr Ser Pro Asn Trp Ala Asp Ser Met Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 874 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 874 Met Asn Asp Gln Thr Ser Glu Val Ser Thr Phe Pro Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 875 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 875 Ser Val Gly Glu Asp His Asn Phe Trp Thr Ser Glu Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 876 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 876 Gln Thr Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 877 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 877 Glu Asn Pro Phe Thr Trp Gln Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 878 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 878 Val Thr Pro Phe Thr Trp Glu Asp Ser Asn Val Phe Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 879 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 879 Gln Ile Pro Phe Thr Trp Glu Gln Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 880 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 880 Gln Ala Pro Leu Thr Trp Gln Glu Ser Ala Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 881<211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 881 Glu Pro Thr Phe Thr Trp Glu Glu Ser Lys Ala Thr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 882 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 882 Thr Thr Thr Leu Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 883 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 883 Glu Ser Pro Leu Thr Trp Glu Glu Ser Ser Ala Leu Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 884<211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 884 Glu Thr Pro Leu Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 885 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 885 Glu Ala Thr Phe Thr Trp Ala Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 886 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 886 Glu Ala Leu Phe Thr Trp Lys Glu Ser Thr Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 887 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 887 Ser Thr Pro Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro Tyr 1 5 10 15 Ala Leu Pro Leu 20 <210> SEQ ID NO 888 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 888 Glu Thr Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 889 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 889 Lys Ala Pro Phe Thr Trp Glu Glu Ser Gln Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 890 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 890 Ser Thr Ser Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 891 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 891 Asp Ser Thr Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 892 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 892 Tyr Ile Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 893 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 893 Gln Thr Ala Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 894 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 894 Glu Thr Leu Phe Thr Trp Glu Glu Ser Asn Ala Thr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 895 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 895 Val Ser Ser Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 896 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 896 Gln Pro Tyr Ala Leu Pro Leu 1 5 <210> SEQ ID NO 897 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is a phosphotyrosyl residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Position 2, Xaa is a 1-napthylalanyl residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is an azetidine residue<400> SEQUENCE: 897 Xaa Xaa Pro Tyr Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 898 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 898 Thr Ala Asn Val Ser Ser Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 899 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 899 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 900 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 900 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 901 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 901 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 902 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 902 Glu Thr Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 903 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (13)..(13) <223> OTHER INFORMATION: Position 13, Xaa is an azetidine residue<400> SEQUENCE: 903 Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Xaa Tyr Ala Leu 1 5 10 15 Pro Leu <210> SEQ ID NO 904 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 904 Ala Asp Val Leu Tyr Trp Gln Pro Tyr Ala Pro Val Thr Leu Trp Val 1 5 10 15 <210> SEQ ID NO 905 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST <400> SEQUENCE: 905 Gly Asp Val Ala Glu Tyr Trp Gln Pro Tyr Ala Leu Pro Leu Thr Ser 1 5 10 15 Leu <210> SEQ ID NO 906 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 906 Ser Trp Thr Asp Tyr Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Ile Ser 1 5 10 15 Gly Leu <210> SEQ ID NO 907 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1, 2, 7)..(8) <223> OTHER INFORMATION: Xaa is any amino acid <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is prolyl or an azetidineresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is S, A, V or L<400> SEQUENCE: 907 Xaa Xaa Gln Xaa Tyr Xaa Xaa Xaa 1 5 <210> SEQ ID NO 908 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is Y, W or F<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 7)..(8) <223> OTHER INFORMATION: Xaa is any amino acid <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is prolyl or an azetidineresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is S, A, V or L<400> SEQUENCE: 908 Xaa Xaa Gln Xaa Tyr Xaa Xaa Xaa 1 5 <210> SEQ ID NO 909 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is Y, W or F<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Position 2, Xaa is E, F, V, W or Y<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is prolyl or an azetidineresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is S, A, V or L<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Position 7, Xaa is M, F, V, R, Q, K, T, S, D,L, I or E <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(8) <223> OTHER INFORMATION: Position 8, Xaa is E, L, W, V, H, I, G, A, D,L, Y, N, Q or P <400> SEQUENCE: 909 Xaa Xaa Gly Xaa Tyr Xaa Xaa Xaa 1 5 <210> SEQ ID NO 910 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is V, L, I, E, P, G, Y, M, T orD <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Position 2, Xaa is Y, W or F<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa is E, F, V, W or Y<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is prolyl or an azetidineresidue; <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Position 7, Xaa is S, A, V or L<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(8) <223> OTHER INFORMATION: Position 8, Xaa is M, F, V, R, Q, K, T, S, D,L, I or E; <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Position 9, Xaa is E, L, W, V, H, I, G, A, D,L, Y, N, Q or P <400> SEQUENCE: 910 Xaa Xaa Xaa Gln Xaa Tyr Xaa Xaa Xaa 1 5 <210> SEQ ID NO 911 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 911 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 912 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 912 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 913 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 913 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 914 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 914 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 915 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 915 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 916 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 916 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 917 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa is A, D, E, F, G, K, Q, S, T,V or Y <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Position 2, Xaa is A, D, G, I, N, P, S, T, V orW <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa is A, D, G, L, N, P, S, T, W orY <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is A, D, E, F, L, N, R, V or Y<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is A, D, E, Q, R, S or T<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is H, I, L, P, S, T or W<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Position 7, Xaa is A, E, F, K, N, Q, R, S or Y;<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(8) <223> OTHER INFORMATION: Position 8, Xaa is D, E, F, Q, R, T or W<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Position 9, Xaa is A, D, P, S, T or W<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is A, D, G, K, N, Q, S or T<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11, Xaa is A, E, L, P, S, T, V or Y<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (12)..(12) <223> OTHER INFORMATION: Position 12, Xaa is V, L, I, E, P, G, Y, M, Tor D <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (13)..(13) <223> OTHER INFORMATION: Position 13, Xaa is Y, W or F<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (14)..(14) <223> OTHER INFORMATION: Position 14, Xaa is E, F, V, W or Y<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16)..(16) <223> OTHER INFORMATION: Position 16, Xaa is P or an azetidine residue;<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18)..(18) <223> OTHER INFORMATION: Position 18, Xaa is S, A, V or L<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (19)..(19) <223> OTHER INFORMATION: Position 19, Xaa is M, F, V, R, Q, K, T, S, D,L, I or E <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (20)..(20) <223> OTHER INFORMATION: Position 20, Xaa is Q or P.<400> SEQUENCE: 917 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gln Xaa 1 5 10 15 Tyr Xaa Xaa Xaa Leu 20 <210> SEQ ID NO 918 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 918 Thr Ala Asn Val Ser Ser Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 919 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 919 Ser Trp Thr Asp Tyr Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Ile Ser 1 5 10 15 Gly Leu <210> SEQ ID NO 920 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 920 Glu Thr Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 921 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 921 Glu Asn Thr Tyr Ser Pro Asn Trp Ala Asp Ser Met Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 922 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 922 Ser Val Gly Glu Asp His Asn Phe Trp Thr Ser Glu Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 923 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 923 Asp Gly Tyr Asp Arg Trp Arg Gln Ser Gly Glu Arg Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 924 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 924 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 925 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 925 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr 1 5 10 <210> SEQ ID NO 926 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 926 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 927 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 927 Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr 1 5 10 <210> SEQ ID NO 928 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 928 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 929 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 929 Ala Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 930 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 930 Phe Ala Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 931 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 931 Phe Glu Ala Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 932 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 932 Phe Glu Trp Ala Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 933 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 933 Phe Glu Trp Thr Ala Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 934 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 934 Phe Glu Trp Thr Pro Ala Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 935 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 935 Phe Glu Trp Thr Pro Gly Ala Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 936 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 936 Phe Glu Trp Thr Pro Gly Tyr Ala Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 937 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 937 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Ala 1 5 10 <210> SEQ ID NO 938 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 938 Phe Glu Trp Thr Gly Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 939 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 5, D aminoacid residue Position 10, Xaa is an azetidine residue <400> SEQUENCE: 939 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 940 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 940 Phe Glu Trp Thr Xaa Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 941 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is a pipecolic acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 941 Phe Glu Trp Thr Xaa Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 942 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is an aminoisobutyric acidresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 942 Phe Glu Trp Thr Pro Xaa Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 943 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is a sarcosine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 943 Phe Glu Trp Thr Pro Xaa Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 944 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa is a sarcosine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 944 Phe Glu Trp Thr Xaa Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 945 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 945 Phe Glu Trp Thr Pro Asn Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 946 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, D amino acid residue<400> SEQUENCE: 946 Phe Glu Trp Thr Pro Val Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 947 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 947 Phe Glu Trp Thr Val Pro Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 948 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 948 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 949 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 949 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 950 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = 1-naphthylalanine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 950 Xaa Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 951 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, xaa is an azetidine residue<400> SEQUENCE: 951 Tyr Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 952 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 952 Phe Glu Trp Val Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 953 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 953 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 954 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 954 Phe Glu Trp Thr Pro Ser Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 955 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 955 Phe Glu Trp Thr Pro Asn Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 956 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = naphthylalanine<400> SEQUENCE: 956 Ser His Leu Tyr Xaa Gln Pro Tyr Ser Val Gln Met 1 5 10 <210> SEQ ID NO 957 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = naphthylalanine<400> SEQUENCE: 957 Thr Leu Val Tyr Xaa Gln Pro Tyr Ser Leu Gln Thr 1 5 10 <210> SEQ ID NO 958 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = naphthylalanine<400> SEQUENCE: 958 Arg Gly Asp Tyr Xaa Gln Pro Tyr Ser Val Gln Ser 1 5 10 <210> SEQ ID NO 959 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = naphthylalanine<400> SEQUENCE: 959 Asn Met Val Tyr Xaa Gln Pro Tyr Ser Ile Gln Thr 1 5 10 <210> SEQ ID NO 960 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 960 Val Tyr Trp Gln Pro Tyr Ser Val Gln 1 5 <210> SEQ ID NO 961 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa = naphthylalanine<400> SEQUENCE: 961 Val Tyr Xaa Gln Pro Tyr Ser Val Gln 1 5 <210> SEQ ID NO 962 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Position 7, Xaa is an azetidine residue<400> SEQUENCE: 962 Thr Phe Val Tyr Trp Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 963 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11, Xaa = p-benzoyl-L-phenylalanine<400> SEQUENCE: 963 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Xaa 1 5 10 <210> SEQ ID NO 964 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11, Xaa = p-benzoyl-L-phenylalanine.<400> SEQUENCE: 964 Xaa Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Xaa 1 5 10 <210> SEQ ID NO 965 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(10) <223> OTHER INFORMATION: Position 8, Xaa = p-benzoyl-L-phenylalanine Position 10, Xaa is an azetidine residue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue<400> SEQUENCE: 965 Phe Glu Trp Thr Pro Gly Tyr Xaa Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 966 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(8) <223> OTHER INFORMATION: Position 8, Xaa = p-benzoyl-L-phenylalanine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue.<400> SEQUENCE: 966 Phe Glu Trp Thr Pro Gly Tyr Xaa Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 967 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Position 7, Xaa = p-benzoyl-L-phenylalanine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue.<400> SEQUENCE: 967 Phe Glu Trp Thr Pro Gly Xaa Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 968 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Position 7, Xaa = p-benzoyl-L-phenylalanine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue.<400> SEQUENCE: 968 Phe Glu Trp Thr Pro Gly Xaa Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 969 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa = p-benzoyl-L-phenylalanine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue.<400> SEQUENCE: 969 Phe Glu Xaa Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 970 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa = p-benzoyl-L-phenylalanine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue.<400> SEQUENCE: 970 Phe Glu Xaa Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 971 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = p-benzoyl-L-phenylalanine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue.<400> SEQUENCE: 971 Xaa Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 972 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = acetylatedp-benzoyl-L-phenylalanine <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa is an azetidine residue.<400> SEQUENCE: 972 Xaa Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 973 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 973 Val Tyr Trp Gln Pro Tyr Ser Val Gln 1 5 <210> SEQ ID NO 974 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 974 Arg Leu Val Tyr Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 975 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = naphthylalanine<400> SEQUENCE: 975 Arg Leu Val Tyr Xaa Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 976 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 976 Arg Leu Asp Tyr Trp Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 977 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 977 Arg Leu Val Trp Phe Gln Pro Tyr Ser Val Gln Arg 1 5 10 <210> SEQ ID NO 978 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 978 Arg Leu Val Tyr Trp Gln Pro Tyr Ser Ile Gln Arg 1 5 10 <210> SEQ ID NO 979 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = D or Y<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa = D or S<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa = S, T or A<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Position 5, Xaa = S or W<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa = S or Y<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7)..(7) <223> OTHER INFORMATION: Xaa is any amino acid <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8)..(8) <223> OTHER INFORMATION: Position 8, Xaa = N, S, K, H or W<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9)..(9) <223> OTHER INFORMATION: Position 9, Xaa = F or L<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = D, N, S or L<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Position 11, Xaa = L, I, Q, M or A.<400> SEQUENCE: 979 Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 1 5 10 <210> SEQ ID NO 980 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 980 Asp Asn Ser Ser Trp Tyr Asp Ser Phe Leu Leu 1 5 10 <210> SEQ ID NO 981 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 981 Asp Asn Thr Ala Trp Tyr Glu Ser Phe Leu Ala 1 5 10 <210> SEQ ID NO 982 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 982 Asp Asn Thr Ala Trp Tyr Glu Asn Phe Leu Leu 1 5 10 <210> SEQ ID NO 983 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 983 Pro Ala Arg Glu Asp Asn Thr Ala Trp Tyr Asp Ser Phe Leu Ile Trp 1 5 10 15 Cys <210> SEQ ID NO 984 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 984 Thr Ser Glu Tyr Asp Asn Thr Thr Trp Tyr Glu Lys Phe Leu Ala Ser 1 5 10 15 Gln <210> SEQ ID NO 985 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 985 Ser Gln Ile Pro Asp Asn Thr Ala Trp Tyr Gln Ser Phe Leu Leu His 1 5 10 15 Gly <210> SEQ ID NO 986 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 986 Ser Pro Phe Ile Asp Asn Thr Ala Trp Tyr Glu Asn Phe Leu Leu Thr 1 5 10 15 Tyr <210> SEQ ID NO 987 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 987 Glu Gln Ile Tyr Asp Asn Thr Ala Trp Tyr Asp His Phe Leu Leu Ser 1 5 10 15 Tyr <210> SEQ ID NO 988 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 988 Thr Pro Phe Ile Asp Asn Thr Ala Trp Tyr Glu Asn Phe Leu Leu Thr 1 5 10 15 Tyr <210> SEQ ID NO 989 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 989 Thr Tyr Thr Tyr Asp Asn Thr Ala Trp Tyr Glu Arg Phe Leu Met Ser 1 5 10 15 Tyr <210> SEQ ID NO 990 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 990 Thr Met Thr Gln Asp Asn Thr Ala Trp Tyr Glu Asn Phe Leu Leu Ser 1 5 10 15 Tyr <210> SEQ ID NO 991 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 991 Thr Ile Asp Asn Thr Ala Trp Tyr Ala Asn Leu Val Gln Thr Tyr Pro 1 5 10 15 Gln <210> SEQ ID NO 992 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 992 Thr Ile Asp Asn Thr Ala Trp Tyr Glu Arg Phe Leu Ala Gln Tyr Pro 1 5 10 15 Asp <210> SEQ ID NO 993 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 993 His Ile Asp Asn Thr Ala Trp Tyr Glu Asn Phe Leu Leu Thr Tyr Thr 1 5 10 15 Pro <210> SEQ ID NO 994 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 994 Ser Gln Asp Asn Thr Ala Trp Tyr Glu Asn Phe Leu Leu Ser Tyr Lys 1 5 10 15 Ala <210> SEQ ID NO 995 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 995 Gln Ile Asp Asn Thr Ala Trp Tyr Glu Arg Phe Leu Leu Gln Tyr Asn 1 5 10 15 Ala <210> SEQ ID NO 996 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 996 Asn Gln Asp Asn Thr Ala Trp Tyr Glu Ser Phe Leu Leu Gln Tyr Asn 1 5 10 15 Thr <210> SEQ ID NO 997 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 997 Thr Ile Asp Asn Thr Ala Trp Tyr Glu Asn Phe Leu Leu Asn His Asn 1 5 10 15 Leu <210> SEQ ID NO 998 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 998 His Tyr Asp Asn Thr Ala Trp Tyr Glu Arg Phe Leu Gln Gln Gly Trp 1 5 10 15 His <210> SEQ ID NO 999 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 999 Glu Thr Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 1000<211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 1000 Tyr Ile Pro Phe Thr Trp Glu Glu Ser Asn Ala Tyr Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 1001 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 1001 Asp Gly Tyr Asp Arg Trp Arg Gln Ser Gly Glu Arg Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 1002 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1, Xaa = phosphotyrosine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Position 2, Xaa = naphthylalanine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa = phosphotyrosine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, Xaa is an azetidine residue.<400> SEQUENCE: 1002 Xaa Xaa Xaa Gln Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 <210> SEQ ID NO 1003 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 1003 Thr Ala Asn Val Ser Ser Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 1004 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1004 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 1005 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 1005 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Leu Ser 1 5 10 15 Asp <210> SEQ ID NO 1006 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1006 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 1007 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1007 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1008 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1008 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1009 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 1 is acetylatedPhe Position 10, Xaa = azetidine <400> SEQUENCE: 1009 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1010 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1010 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1011 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1011 Phe Glu Trp Thr Pro Ala Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1012 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1012 Phe Glu Trp Thr Pro Ala Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1013 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1013 Phe Glu Trp Thr Pro Ala Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1014 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1014 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 1015 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1015 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 1016 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1016 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr Ala Leu Pro Leu 1 5 10 15 <210> SEQ ID NO 1017 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <400> SEQUENCE: 1017 Thr Ala Asn Val Ser Ser Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro 1 5 10 15 Tyr Ala Leu Pro Leu 20 <210> SEQ ID NO 1018 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<400> SEQUENCE: 1018 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1019 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1019 Phe Glu Trp Thr Pro Gly Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1020 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine<400> SEQUENCE: 1020 Phe Glu Trp Thr Pro Gly Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1021 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, D amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine.<400> SEQUENCE: 1021 Phe Glu Trp Thr Pro Ala Tyr Trp Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1022 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, D amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine.<400> SEQUENCE: 1022 Phe Glu Trp Thr Pro Ala Trp Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1023 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Position 1 is acetylated Phe<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Position 6, D amino acid residue<220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Position 10, Xaa = azetidine.<400> SEQUENCE: 1023 Phe Glu Trp Thr Pro Ala Tyr Tyr Gln Xaa Tyr 1 5 10 <210> SEQ ID NO 1024 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1024 Gly Gly Leu Tyr Leu Cys Arg Phe Gly Pro Val Thr Trp Asp Cys Gly 1 5 10 15 Tyr Lys Gly Gly 20 <210> SEQ ID NO 1025 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1025 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly 20 <210> SEQ ID NO 1026 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1026 Gly Gly Asp Tyr His Cys Arg Met Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Leu Gly Gly 20 <210> SEQ ID NO 1027 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <400> SEQUENCE: 1027 Val Glu Pro Asn Cys Asp Ile His Val Met Trp Glu Trp Glu Cys Phe 1 5 10 15 Glu Arg Leu <210> SEQ ID NO 1028 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR <400> SEQUENCE: 1028 Cys Thr Thr His Trp Gly Phe Thr Leu Cys 1 5 10 <210> SEQ ID NO 1029 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1029 Val Gly Asn Tyr Met Cys His Phe Gly Pro Ile Thr Trp Val Cys Arg 1 5 10 15 Pro Gly Gly Gly 20 <210> SEQ ID NO 1030 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1030 Gly Gly Val Tyr Ala Cys Arg Met Gly Pro Ile Thr Trp Val Cys Ser 1 5 10 15 Pro Leu Gly Gly 20 <210> SEQ ID NO 1031 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF- ANTAGONIST <400> SEQUENCE: 1031 Arg Gly Trp Val Glu Ile Cys Ala Ala Asp Asp Tyr Gly Arg Cys Leu 1 5 10 15 Thr Glu Ala Gln 20 <210> SEQ ID NO 1032 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Fc domain attached at Position 1 of theN-terminus <400> SEQUENCE: 1032 Gly Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala 1 5 10 15 Ala Arg Ala <210> SEQ ID NO 1033 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TPO-MIMETIC <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (19)..(19) <223> OTHER INFORMATION: Fc domain attached at Position 19 of theC-terminus <400> SEQUENCE: 1033 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Gly Gly <210> SEQ ID NO 1034 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (25)..(25) <223> OTHER INFORMATION: Fc domain attached at Position 25 of the C-terminus <400> SEQUENCE: 1034 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln Gly Gly Gly Gly Gly Gly Gly 20 25 <210> SEQ ID NO 1035 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1035 Val Gly Asn Tyr Met Ala His Met Gly Pro Ile Thr Trp Val Cys Arg 1 5 10 15 Pro Gly Gly <210> SEQ ID NO 1036 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1036 Gly Gly Thr Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 15 Pro Gln <210> SEQ ID NO 1037 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1037 Gly Gly Leu Tyr Ala Cys His Met Gly Pro Met Thr Trp Val Cys Gln 1 5 10 15 Pro Leu Arg Gly 20 <210> SEQ ID NO 1038 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1038 Thr Ile Ala Gln Tyr Ile Cys Tyr Met Gly Pro Glu Thr Trp Glu Cys 1 5 10 15 Arg Pro Ser Pro Lys Ala 20 <210> SEQ ID NO 1039 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1039 Tyr Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 <210> SEQ ID NO 1040 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1040 Tyr Cys His Phe Gly Pro Leu Thr Trp Val Cys 1 5 10 <210> SEQ ID NO 1041 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <400> SEQUENCE: 1041 Ser Cys His Phe Gly Pro Leu Thr Trp Val Cys Lys 1 5 10 <210> SEQ ID NO 1042 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: EPO-MIMETIC PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Xaa (Pos1) can be any one of the 20 L-amino acids; except Xaa (Pos1) may/may not be Y and Xaa (Pos1) may be any non-naturally occurring aromatic acid analog when Xaa (Pos1) is Y. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(8) <223> OTHER INFORMATION: Xaa (Pos2, 8) can be any one of the 20 L-amino acids <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Xaa (Pos3) can be C, A, a-amino-y-bromobutyric acid or Hoc; <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Xaa (Pos4) can be R, H, L or W <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (5)..(5) <223> OTHER INFORMATION: Xaa (Pos5) can be M, F or I <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (10)..(10) <223> OTHER INFORMATION: Xaa is any amino acid <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (11)..(11) <223> OTHER INFORMATION: Xaa (Pos11) can be D, E, I, L or V <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (12)..(12) <223> OTHER INFORMATION: Xaa (Pos12) can be C, A, a-amino-y-bromobutyric acid or Hoc provided that either Xaa (Pos3, 12) is C or Hoc. <400> SEQUENCE: 1042 Xaa Xaa Xaa Xaa Gly Pro Xaa Thr Trp Xaa Xaa 1 5 10 <210> SEQ ID NO 1043 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(4) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 1043 Asp Leu Xaa Xaa Leu 1 5 <210> SEQ ID NO 1044 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1044 Arg Thr Asp Leu Asp Ser Leu Arg Thr Tyr Thr Leu 1 5 10 <210> SEQ ID NO 1045 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF-ALPHA INHIBITOR <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Fc domain attached at Position 1 of theN-terminus <400> SEQUENCE: 1045 Gly Gly Gly Gly Gly Asp Phe Leu Pro His Tyr Lys Asn Thr Ser Leu 1 5 10 15 Gly His Arg Pro 20 <210> SEQ ID NO 1046 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF-ALPHA INHIBITOR <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (20)..(20) <223> OTHER INFORMATION: Fc domain attached at Position 20 of theC-terminus <400> SEQUENCE: 1046 Asp Phe Leu Pro His Tyr Lys Asn Thr Ser Leu Gly His Arg Pro Gly 1 5 10 15 Gly Gly Gly Gly 20 <210> SEQ ID NO 1047 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Fc domain attached at Position 1 of theN-terminus <400> SEQUENCE: 1047 Gly Gly Gly Gly Gly Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr 1 5 10 15 Ala Leu Pro Leu 20 <210> SEQ ID NO 1048 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (20)..(20) <223> OTHER INFORMATION: Fc domain attached at Position 20 of theC-terminus <400> SEQUENCE: 1048 Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Leu Gly 1 5 10 15 Gly Gly Gly Gly 20 <210> SEQ ID NO 1049 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Fc domain attached at Position 1 of theN-terminus <400> SEQUENCE: 1049 Gly Gly Gly Gly Gly Val Glu Pro Asn Cys Asp Ile His Val Met Trp 1 5 10 15 Glu Trp Glu Cys Phe Glu Arg Leu 20 <210> SEQ ID NO 1050 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (24)..(24) <223> OTHER INFORMATION: Fc domain attached at Position 24 of the C-terminus <400> SEQUENCE: 1050 Val Glu Pro Asn Cys Asp Ile His Val Met Trp Glu Trp Glu Cys Phe 1 5 10 15 Glu Arg Leu Gly Gly Gly Gly Gly 20 <210> SEQ ID NO 1051 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Fc domain attached at Position 1 of theN-terminus <400> SEQUENCE: 1051 Gly Gly Gly Gly Gly Cys Thr Thr His Trp Gly Phe Thr Leu Cys 1 5 10 15 <210> SEQ ID NO 1052 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15)..(15) <223> OTHER INFORMATION: Fc domain attached at Position 15 of theC-terminus <400> SEQUENCE: 1052 Cys Thr Thr His Trp Gly Phe Thr Leu Cys Gly Gly Gly Gly Gly 1 5 10 15 <210> SEQ ID NO 1053 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1053 Arg Thr Asp Leu Asp Ser Leu Arg Thr Tyr 1 5 10 <210> SEQ ID NO 1054 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1054 Arg Thr Asp Leu Asp Ser Leu Arg Thr 1 5 <210> SEQ ID NO 1055 <211> LENGTH: 757 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: FC-TNF-ALPA INHIBITORS <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (4)..(747) <223> OTHER INFORMATION: <400> SEQUENCE: 1055 cat atg gac aaa act cac aca tgt cca cct tgt cca gct ccg gaa ctc 48 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 1 5 10 15 ctg ggg gga ccg tca gtc ttc ctc ttc ccc cca aaa ccc aag gac acc 96 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 20 25 30 ctc atg atc tcc cgg acc cct gag gtc aca tgc gtg gtg gtg gac gtg 144 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 35 40 45 agc cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg 192 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 50 55 60 gag gtg cat aat gcc aag aca aag ccg cgg gag gag cag tac aac agc 240 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 65 70 75 acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg 288 Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 80 85 90 95 aat ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc 336 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 100 105 110 ccc atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca 384 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 115 120 125 cag gtg tac acc ctg ccc cca tcc cgg gat gag ctg acc aag aac cag 432 Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 130 135 140 gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc 480Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 145 150 155 gtg gag tgg gag agc aat ggg cag ccg gag aac aac tac aag acc acg 528 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 160 165 170 175 cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc 576 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 180 185 190 acc gtg gac aag agc agg tgg cag cag ggg aac gtc ttc tca tgc tcc 624 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 195 200 205 gtg atg cat gag gct ctg cac aac cac tac acg cag aag agc ctc tcc 672 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 210 215 220 ctg tct ccg ggt aaa ggt gga ggt ggt ggt gac ttc ctg ccg cac tac 720Leu Ser Pro Gly Lys Gly Gly Gly Gly Gly Asp Phe Leu Pro His Tyr 225 230 235 aaa aac acc tct ctg ggt cac cgt ccg taatggatcc 757 Lys Asn Thr Ser Leu Gly His Arg Pro 240 245 <210> SEQ ID NO 1056 <211> LENGTH: 248 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: FC-TNF-ALPA INHIBITORS <400> SEQUENCE: 1056 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys Gly Gly Gly Gly Gly Asp Phe Leu Pro His Tyr Lys 225 230 235 240 Asn Thr Ser Leu Gly His Arg Pro 245 <210> SEQ ID NO 1057 <211> LENGTH: 761 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF-ALPHA INHIBITOR-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (4)..(747) <223> OTHER INFORMATION: <400> SEQUENCE: 1057 cat atg gac ttc ctg ccg cac tac aaa aac acc tct ctg ggt cac cgt 48 Met Asp Phe Leu Pro His Tyr Lys Asn Thr Ser Leu Gly His Arg 1 5 10 15 ccg ggt gga ggc ggt ggg gac aaa act cac aca tgt cca cct tgc cca 96 Pro Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro 20 25 30 gca cct gaa ctc ctg ggg gga ccg tca gtt ttc ctc ttc ccc cca aaa 144 Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 35 40 45 ccc aag gac acc ctc atg atc tcc cgg acc cct gag gtc aca tgc gtg 192 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 50 55 60 gtg gtg gac gtg agc cac gaa gac cct gag gtc aag ttc aac tgg tac 240Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 65 70 75 gtg gac ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg gag gag 288 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 80 85 90 95 cag tac aac agc acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac 336 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 100 105 110 cag gac tgg ctg aat ggc aag gag tac aag tgc aag gtc tcc aac aaa 384 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 115 120 125 gcc ctc cca gcc ccc atc gag aaa acc atc tcc aaa gcc aaa ggg cag 432 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 130 135 140 ccc cga gaa cca cag gtg tac acc ctg ccc cca tcc cgg gat gag ctg 480Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 145 150 155 acc aag aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc 528 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 160 165 170 175 agc gac atc gcc gtg gag tgg gag agc aat ggg cag ccg gag aac aac 576 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 180 185 190 tac aag acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc 624 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 195 200 205 tac agc aag ctc acc gtg gac aag agc agg tgg cag cag ggg aac gtc 672 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 210 215 220 ttc tca tgc tcc gtg atg cat gag gct ctg cac aac cac tac acg cag 720Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 225 230 235 aag agc ctc tcc ctg tct ccg ggt aaa taatggatcc gcgg 761Lys Ser Leu Ser Leu Ser Pro Gly Lys 240 245 <210> SEQ ID NO 1058 <211> LENGTH: 248 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF-ALPHA INHIBITOR-Fc <400> SEQUENCE: 1058 Met Asp Phe Leu Pro His Tyr Lys Asn Thr Ser Leu Gly His Arg Pro 1 5 10 15 Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 20 25 30 Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 35 40 45 Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 50 55 60 Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 65 70 75 80 Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 85 90 95 Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 100 105 110 Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 115 120 125 Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 130 135 140 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 145 150 155 160 Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 165 170 175 Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 180 185 190 Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 195 200 205 Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 210 215 220 Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 225 230 235 240 Ser Leu Ser Leu Ser Pro Gly Lys 245 <210> SEQ ID NO 1059 <211> LENGTH: 763 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: FC-IL-1 ANTAGONIST <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (4)..(747) <223> OTHER INFORMATION: <400> SEQUENCE: 1059 cat atg gac aaa act cac aca tgt cca cct tgt cca gct ccg gaa ctc 48 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 1 5 10 15 ctg ggg gga ccg tca gtc ttc ctc ttc ccc cca aaa ccc aag gac acc 96 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 20 25 30 ctc atg atc tcc cgg acc cct gag gtc aca tgc gtg gtg gtg gac gtg 144 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 35 40 45 agc cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg 192 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 50 55 60 gag gtg cat aat gcc aag aca aag ccg cgg gag gag cag tac aac agc 240 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 65 70 75 acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg 288 Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 80 85 90 95 aat ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc 336 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 100 105 110 ccc atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca 384 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 115 120 125 cag gtg tac acc ctg ccc cca tcc cgg gat gag ctg acc aag aac cag 432 Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 130 135 140 gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc 480Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 145 150 155 gtg gag tgg gag agc aat ggg cag ccg gag aac aac tac aag acc acg 528 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 160 165 170 175 cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc 576 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 180 185 190 acc gtg gac aag agc agg tgg cag cag ggg aac gtc ttc tca tgc tcc 624 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 195 200 205 gtg atg cat gag gct ctg cac aac cac tac acg cag aag agc ctc tcc 672 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 210 215 220 ctg tct ccg ggt aaa ggt gga ggt ggt ggt ttc gaa tgg acc ccg ggt 720Leu Ser Pro Gly Lys Gly Gly Gly Gly Gly Phe Glu Trp Thr Pro Gly 225 230 235 tac tgg cag ccg tac gct ctg ccg ctg taatggatcc ctcgag 763Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 240 245 <210> SEQ ID NO 1060 <211> LENGTH: 248 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: FC-IL-1 ANTAGONIST <400> SEQUENCE: 1060 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys Gly Gly Gly Gly Gly Phe Glu Trp Thr Pro Gly Tyr 225 230 235 240 Trp Gln Pro Tyr Ala Leu Pro Leu 245 <210> SEQ ID NO 1061 <211> LENGTH: 757 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST-FC <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (4)..(747) <223> OTHER INFORMATION: <400> SEQUENCE: 1061 cat atg ttc gaa tgg acc ccg ggt tac tgg cag ccg tac gct ctg ccg 48 Met Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr Ala Leu Pro 1 5 10 15 ctg ggt gga ggc ggt ggg gac aaa act cac aca tgt cca cct tgc cca 96 Leu Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro 20 25 30 gca cct gaa ctc ctg ggg gga ccg tca gtt ttc ctc ttc ccc cca aaa 144 Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 35 40 45 ccc aag gac acc ctc atg atc tcc cgg acc cct gag gtc aca tgc gtg 192 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 50 55 60 gtg gtg gac gtg agc cac gaa gac cct gag gtc aag ttc aac tgg tac 240Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 65 70 75 gtg gac ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg gag gag 288 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 80 85 90 95 cag tac aac agc acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac 336 Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 100 105 110 cag gac tgg ctg aat ggc aag gag tac aag tgc aag gtc tcc aac aaa 384 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 115 120 125 gcc ctc cca gcc ccc atc gag aaa acc atc tcc aaa gcc aaa ggg cag 432 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 130 135 140 ccc cga gaa cca cag gtg tac acc ctg ccc cca tcc cgg gat gag ctg 480Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 145 150 155 acc aag aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc 528 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 160 165 170 175 agc gac atc gcc gtg gag tgg gag agc aat ggg cag ccg gag aac aac 576 Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 180 185 190 tac aag acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc 624 Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 195 200 205 tac agc aag ctc acc gtg gac aag agc agg tgg cag cag ggg aac gtc 672 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 210 215 220 ttc tca tgc tcc gtg atg cat gag gct ctg cac aac cac tac acg cag 720Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 225 230 235 aag agc ctc tcc ctg tct ccg ggt aaa taatggatcc 757 Lys Ser Leu Ser Leu Ser Pro Gly Lys 240 245 <210> SEQ ID NO 1062 <211> LENGTH: 248 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST-FC <400> SEQUENCE: 1062 Met Phe Glu Trp Thr Pro Gly Tyr Trp Gln Pro Tyr Ala Leu Pro Leu 1 5 10 15 Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 20 25 30 Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 35 40 45 Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 50 55 60 Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 65 70 75 80 Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 85 90 95 Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 100 105 110 Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 115 120 125 Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 130 135 140 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 145 150 155 160 Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 165 170 175 Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 180 185 190 Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 195 200 205 Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 210 215 220 Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 225 230 235 240 Ser Leu Ser Leu Ser Pro Gly Lys 245 <210> SEQ ID NO 1063 <211> LENGTH: 773 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-VEGF ANTAGONIST <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (4)..(759) <223> OTHER INFORMATION: <400> SEQUENCE: 1063 cat atg gac aaa act cac aca tgt cca ccg tgc cca gca cct gaa ctc 48 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 1 5 10 15 ctg ggg gga ccg tca gtt ttc ctc ttc ccc cca aaa ccc aag gac acc 96 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 20 25 30 ctc atg atc tcc cgg acc cct gag gtc aca tgc gtg gtg gtg gac gtg 144 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 35 40 45 agc cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg 192 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 50 55 60 gag gtg cat aat gcc aag aca aag ccg cgg gag gag cag tac aac agc 240 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 65 70 75 acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg 288 Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 80 85 90 95 aat ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc 336 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 100 105 110 ccc atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca 384 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 115 120 125 cag gtg tac acc ctg ccc cca tcc cgg gat gag ctg acc aag aac cag 432 Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 130 135 140 gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc 480Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 145 150 155 gtg gag tgg gag agc aat ggg cag ccg gag aac aac tac aag acc acg 528 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 160 165 170 175 cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc 576 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 180 185 190 acc gtg gac aag agc agg tgg cag cag ggg aac gtc ttc tca tgc tcc 624 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 195 200 205 gtg atg cat gag gct ctg cac aac cac tac acg cag aag agc ctc tcc 672 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 210 215 220 ctg tct ccg ggt aaa ggt ggt ggt ggt ggt gtt gaa ccg aac tgt gac 720Leu Ser Pro Gly Lys Gly Gly Gly Gly Gly Val Glu Pro Asn Cys Asp 225 230 235 atc cat gtt atg tgg gaa tgg gaa tgt ttt gaa cgt ctg taactcgagg 769 Ile His Val Met Trp Glu Trp Glu Cys Phe Glu Arg Leu 240 245 250 atcc 773<210> SEQ ID NO 1064 <211> LENGTH: 252 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-VEGF ANTAGONIST <400> SEQUENCE: 1064 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys Gly Gly Gly Gly Gly Val Glu Pro Asn Cys Asp Ile 225 230 235 240 His Val Met Trp Glu Trp Glu Cys Phe Glu Arg Leu 245 250 <210> SEQ ID NO 1065 <211> LENGTH: 773 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF ANTAGONIST-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (4)..(759) <223> OTHER INFORMATION: <400> SEQUENCE: 1065 cat atg gtt gaa ccg aac tgt gac atc cat gtt atg tgg gaa tgg gaa 48 Met Val Glu Pro Asn Cys Asp Ile His Val Met Trp Glu Trp Glu 1 5 10 15 tgt ttt gaa cgt ctg ggt ggt ggt ggt ggt gac aaa act cac aca tgt 96 Cys Phe Glu Arg Leu Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys 20 25 30 cca ccg tgc cca gca cct gaa ctc ctg ggg gga ccg tca gtt ttc ctc 144 Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 35 40 45 ttc ccc cca aaa ccc aag gac acc ctc atg atc tcc cgg acc cct gag 192 Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 50 55 60 gtc aca tgc gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc aag 240 Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 65 70 75 ttc aac tgg tac gtg gac ggc gtg gag gtg cat aat gcc aag aca aag 288 Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 80 85 90 95 ccg cgg gag gag cag tac aac agc acg tac cgt gtg gtc agc gtc ctc 336 Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 100 105 110 acc gtc ctg cac cag gac tgg ctg aat ggc aag gag tac aag tgc aag 384 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 115 120 125 gtc tcc aac aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc aaa 432 Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 130 135 140 gcc aaa ggg cag ccc cga gaa cca cag gtg tac acc ctg ccc cca tcc 480Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 145 150 155 cgg gat gag ctg acc aag aac cag gtc agc ctg acc tgc ctg gtc aaa 528 Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 160 165 170 175 ggc ttc tat ccc agc gac atc gcc gtg gag tgg gag agc aat ggg cag 576 Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 180 185 190 ccg gag aac aac tac aag acc acg cct ccc gtg ctg gac tcc gac ggc 624 Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 195 200 205 tcc ttc ttc ctc tac agc aag ctc acc gtg gac aag agc agg tgg cag 672 Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 210 215 220 cag ggg aac gtc ttc tca tgc tcc gtg atg cat gag gct ctg cac aac 720Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 225 230 235 cac tac acg cag aag agc ctc tcc ctg tct ccg ggt aaa taactcgagg 769 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 240 245 250 atcc 773<210> SEQ ID NO 1066 <211> LENGTH: 252 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF ANTAGONIST-Fc <400> SEQUENCE: 1066 Met Val Glu Pro Asn Cys Asp Ile His Val Met Trp Glu Trp Glu Cys 1 5 10 15 Phe Glu Arg Leu Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro 20 25 30 Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 35 40 45 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 50 55 60 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 65 70 75 80 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 85 90 95 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 100 105 110 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 115 120 125 Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 130 135 140 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 145 150 155 160 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 165 170 175 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 180 185 190 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 195 200 205 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 210 215 220 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 225 230 235 240 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 245 250 <210> SEQ ID NO 1067 <211> LENGTH: 748 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc MMP INHIBITOR <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (4)..(732) <223> OTHER INFORMATION: <400> SEQUENCE: 1067 cat atg gac aaa act cac aca tgt cca cct tgt cca gct ccg gaa ctc 48 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 1 5 10 15 ctg ggg gga ccg tca gtc ttc ctc ttc ccc cca aaa ccc aag gac acc 96 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 20 25 30 ctc atg atc tcc cgg acc cct gag gtc aca tgc gtg gtg gtg gac gtg 144 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 35 40 45 agc cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg 192 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 50 55 60 gag gtg cat aat gcc aag aca aag ccg cgg gag gag cag tac aac agc 240 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 65 70 75 acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg 288 Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 80 85 90 95 aat ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc 336 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 100 105 110 ccc atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca 384 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 115 120 125 cag gtg tac acc ctg ccc cca tcc cgg gat gag ctg acc aag aac cag 432 Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 130 135 140 gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc 480Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 145 150 155 gtg gag tgg gag agc aat ggg cag ccg gag aac aac tac aag acc acg 528 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 160 165 170 175 cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc 576 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 180 185 190 acc gtg gac aag agc agg tgg cag cag ggg aac gtc ttc tca tgc tcc 624 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 195 200 205 gtg atg cat gag gct ctg cac aac cac tac acg cag aag agc ctc tcc 672 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 210 215 220 ctg tct ccg ggt aaa ggt gga ggt ggt ggt tgc acc acc cac tgg ggt 720Leu Ser Pro Gly Lys Gly Gly Gly Gly Gly Cys Thr Thr His Trp Gly 225 230 235 ttc acc ctg tgc taatggatcc ctcgag 748Phe Thr Leu Cys 240 <210> SEQ ID NO 1068 <211> LENGTH: 243 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc MMP INHIBITOR <400> SEQUENCE: 1068 Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 1 5 10 15 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 20 25 30 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 35 40 45 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 50 55 60 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 65 70 75 80 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 85 90 95 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 100 105 110 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 115 120 125 Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 130 135 140 Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 145 150 155 160 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 165 170 175 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 180 185 190 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 195 200 205 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 210 215 220 Ser Pro Gly Lys Gly Gly Gly Gly Gly Cys Thr Thr His Trp Gly Phe 225 230 235 240 Thr Leu Cys <210> SEQ ID NO 1069 <211> LENGTH: 763 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR-Fc <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (4)..(753) <223> OTHER INFORMATION: <400> SEQUENCE: 1069 cat atg tgc acc acc cac tgg ggt ttc acc ctg tgc ggt gga ggc ggt 48 Met Cys Thr Thr His Trp Gly Phe Thr Leu Cys Gly Gly Gly Gly 1 5 10 15 ggg gac aaa ggt gga ggc ggt ggg gac aaa act cac aca tgt cca cct 96 Gly Asp Lys Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro 20 25 30 tgc cca gca cct gaa ctc ctg ggg gga ccg tca gtt ttc ctc ttc ccc 144 Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 35 40 45 cca aaa ccc aag gac acc ctc atg atc tcc cgg acc cct gag gtc aca 192 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 50 55 60 tgc gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc aag ttc aac 240Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 65 70 75 tgg tac gtg gac ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg 288 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 80 85 90 95 gag gag cag tac aac agc acg tac cgt gtg gtc agc gtc ctc acc gtc 336 Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 100 105 110 ctg cac cag gac tgg ctg aat ggc aag gag tac aag tgc aag gtc tcc 384 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 115 120 125 aac aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc aaa gcc aaa 432 Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 130 135 140 ggg cag ccc cga gaa cca cag gtg tac acc ctg ccc cca tcc cgg gat 480 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 145 150 155 gag ctg acc aag aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc 528 Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 160 165 170 175 tat ccc agc gac atc gcc gtg gag tgg gag agc aat ggg cag ccg gag 576 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 180 185 190 aac aac tac aag acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc 624 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 195 200 205 ttc ctc tac agc aag ctc acc gtg gac aag agc agg tgg cag cag ggg 672 Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 210 215 220 aac gtc ttc tca tgc tcc gtg atg cat gag gct ctg cac aac cac tac 720Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 225 230 235 acg cag aag agc ctc tcc ctg tct ccg ggt aaa taatggatcc 763 Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 240 245 250 <210> SEQ ID NO 1070 <211> LENGTH: 250 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR-Fc <400> SEQUENCE: 1070 Met Cys Thr Thr His Trp Gly Phe Thr Leu Cys Gly Gly Gly Gly Gly 1 5 10 15 Asp Lys Gly Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys 20 25 30 Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 35 40 45 Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 50 55 60 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 65 70 75 80 Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 85 90 95 Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 100 105 110 His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 115 120 125 Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 130 135 140 Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 145 150 155 160 Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 165 170 175 Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 180 185 190 Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 195 200 205 Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 210 215 220 Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 225 230 235 240 Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 245 250 <210> SEQ ID NO 1071 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1071 Cys Gly Arg Glu Cys Pro Arg Leu Cys Gln Ser Ser Cys 1 5 10 <210> SEQ ID NO 1072 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1072 Cys Asn Gly Arg Cys Val Ser Gly Cys Ala Gly Arg Cys 1 5 10 <210> SEQ ID NO 1073 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1073 Cys Leu Ser Gly Ser Leu Ser Cys 1 5 <210> SEQ ID NO 1074 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1074 Asn Gly Arg Ala His Ala 1 5 <210> SEQ ID NO 1075 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1075 Cys Asn Gly Arg Cys 1 5 <210> SEQ ID NO 1076 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1076 Cys Asp Cys Arg Gly Asp Cys Phe Cys 1 5 <210> SEQ ID NO 1077 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1077 Cys Gly Ser Leu Val Arg Cys 1 5 <210> SEQ ID NO 1078 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1078 Arg Thr Asp Leu Asp Ser Leu Arg 1 5 <210> SEQ ID NO 1079 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1079 Gly Asp Leu Asp Leu Leu Lys Leu Arg Leu Thr Leu 1 5 10 <210> SEQ ID NO 1080 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1080 Gly Asp Leu His Ser Leu Arg Gln Leu Leu Ser Arg 1 5 10 <210> SEQ ID NO 1081 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1081 Arg Asp Asp Leu His Met Leu Arg Leu Gln Leu Trp 1 5 10 <210> SEQ ID NO 1082 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1082 Ser Ser Asp Leu His Ala Leu Lys Lys Arg Tyr Gly 1 5 10 <210> SEQ ID NO 1083 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1083 Arg Gly Asp Leu Lys Gln Leu Ser Glu Leu Thr Trp 1 5 10 <210> SEQ ID NO 1084 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: INTEGRIN-BINDING PEPTIDE <400> SEQUENCE: 1084 Arg Gly Asp Leu Ala Ala Leu Ser Ala Pro Pro Val 1 5 10 <210> SEQ ID NO 1085 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <400> SEQUENCE: 1085 Arg Gly Trp Val Glu Ile Cys Val Ala Asp Asp Asn Gly Met Cys Val 1 5 10 15 Thr Glu Ala Gln 20 <210> SEQ ID NO 1086 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <400> SEQUENCE: 1086 Gly Trp Asp Glu Cys Asp Val Ala Arg Met Trp Glu Trp Glu Cys Phe 1 5 10 15 Ala Gly Val <210> SEQ ID NO 1087 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <400> SEQUENCE: 1087 Arg Gly Trp Val Glu Ile Cys Glu Ser Asp Val Trp Gly Arg Cys Leu 1 5 10 15 <210> SEQ ID NO 1088 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <400> SEQUENCE: 1088 Arg Gly Trp Val Glu Ile Cys Glu Ser Asp Val Trp Gly Arg Cys Leu 1 5 10 15 <210> SEQ ID NO 1089 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <400> SEQUENCE: 1089 Gly Gly Asn Glu Cys Asp Ile Ala Arg Met Trp Glu Trp Glu Cys Phe 1 5 10 15 Glu Arg Leu <210> SEQ ID NO 1090 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF-ANTAGONIST <400> SEQUENCE: 1090 Arg Gly Trp Val Glu Ile Cys Ala Ala Asp Asp Tyr Gly Arg Cys Leu 1 5 10 15 <210> SEQ ID NO 1091 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (6)..(6) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 1091 Cys Leu Arg Ser Gly Xaa Gly Cys 1 5 <210> SEQ ID NO 1092 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 3, 8)..(9) <223> OTHER INFORMATION: Xaa = any amino acid. <400> SEQUENCE: 1092 Cys Xaa Xaa His Trp Gly Phe Xaa Xaa Cys 1 5 10 <210> SEQ ID NO 1093 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(4) <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 1093 Cys Xaa Pro Xaa Cys 1 5 <210> SEQ ID NO 1094 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR <400> SEQUENCE: 1094 Cys Arg Arg His Trp Gly Phe Glu Phe Cys 1 5 10 <210> SEQ ID NO 1095 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR <400> SEQUENCE: 1095 Ser Thr Thr His Trp Gly Phe Thr Leu Ser 1 5 10 <210> SEQ ID NO 1096 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CTLA4-MIMETIC <400> SEQUENCE: 1096 Cys Ser Leu His Trp Gly Phe Trp Trp Cys 1 5 10 <210> SEQ ID NO 1097 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CARBOHYDRATE (GD1 ALPHA) MIMETIC <400> SEQUENCE: 1097 Trp His Trp Arg His Arg Ile Pro Leu Gln Leu Ala Ala Gly Arg 1 5 10 15 <210> SEQ ID NO 1098 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1098 Leu Lys Thr Pro Arg Val 1 5 <210> SEQ ID NO 1099 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1099 Asn Thr Leu Lys Thr Pro Arg Val 1 5 <210> SEQ ID NO 1100 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1100 Asn Thr Leu Lys Thr Pro Arg Val Gly Gly Cys 1 5 10 <210> SEQ ID NO 1101 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1101 Lys Asp Lys Ala Thr Phe 1 5 <210> SEQ ID NO 1102 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1102 Lys Asp Lys Ala Thr Phe Gly Cys His Asp 1 5 10 <210> SEQ ID NO 1103 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1103 Lys Asp Lys Ala Thr Phe Gly Cys His Asp Gly Cys 1 5 10 <210> SEQ ID NO 1104 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1104 Thr Leu Arg Val Tyr Lys 1 5 <210> SEQ ID NO 1105 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1105 Ala Thr Leu Arg Val Tyr Lys Gly Gly 1 5 <210> SEQ ID NO 1106 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: BETA2GPI AB BINDING <400> SEQUENCE: 1106 Cys Ala Thr Leu Arg Val Tyr Lys Gly Gly 1 5 10 <210> SEQ ID NO 1107 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MEMBRANE-TRANSPORTING <400> SEQUENCE: 1107 Ile Asn Leu Lys Ala Leu Ala Ala Leu Ala Lys Lys Ile Leu 1 5 10 <210> SEQ ID NO 1108 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MEMBRANE-TRANSPORTING <400> SEQUENCE: 1108 Gly Trp Thr Leu Asn Ser Ala Gly Tyr Leu Leu Gly 1 5 10 <210> SEQ ID NO 1109 <211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MEMBRANE-TRANSPORTING <400> SEQUENCE: 1109 Gly Trp Thr Leu Asn Ser Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu 1 5 10 15 Lys Ala Leu Ala Ala Leu Ala Lys Lys Ile Leu 20 25 <210> SEQ ID NO 1110 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc VEGF ANTAGONIST <400> SEQUENCE: 1110 gttgaaccga actgtgacat ccatgttatg tgggaatggg aatgttttga acgtctg 57 <210> SEQ ID NO 1111 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc VEGF ANTAGONIST <400> SEQUENCE: 1111 cagacgttca aaacattccc attcccacat aacatggatg tcacagttcg gttcaac 57 <210> SEQ ID NO 1112 <211> LENGTH: 81 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc-TNA-ALPHA INHIBITORS <400> SEQUENCE: 1112 ccgcggatcc attacggacg gtgacccaga gaggtgtttt tgtagtgcgg caggaagtca 60ccaccacctc cacctttacc c 81<210> SEQ ID NO 1113 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc VEGF ANTAGONIST <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)..(57) <223> OTHER INFORMATION: <400> SEQUENCE: 1113 gtt gaa ccg aac tgt gac atc cat gtt atg tgg gaa tgg gaa tgt ttt 48 Val Glu Pro Asn Cys Asp Ile His Val Met Trp Glu Trp Glu Cys Phe 1 5 10 15 gaa cgt ctg 57 Glu Arg Leu <210> SEQ ID NO 1114 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc VEGF ANTAGONIST <400> SEQUENCE: 1114 Val Glu Pro Asn Cys Asp Ile His Val Met Trp Glu Trp Glu Cys Phe 1 5 10 15 Glu Arg Leu <210> SEQ ID NO 1115 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc MMP INHIBITOR <400> SEQUENCE: 1115 ccgcggatcc attagcacag ggtgaaaccc cagtgggtgg tgcaaccacc acctccacct 60 ttaccc 66 <210> SEQ ID NO 1116 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: MMP INHIBITOR Fc <400> SEQUENCE: 1116 gaataacata tgtgcaccac ccactggggt ttcaccctgt gcggtggagg cggtggggac 60aaa 63 <210> SEQ ID NO 1117 <211> LENGTH: 81 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TNF-ALPHA INHIBITOR Fc <400> SEQUENCE: 1117 gaataacata tggacttcct gccgcactac aaaaacacct ctctgggtca ccgtccgggt 60 ggaggcggtg gggacaaaac t 81<210> SEQ ID NO 1118 <211> LENGTH: 81 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc IL-1 ANTAGONIST <400> SEQUENCE: 1118 ccgcggatcc attacagcgg cagagcgtac ggctgccagt aacccggggt ccattcgaaa 60 ccaccacctc cacctttacc c 81<210> SEQ ID NO 1119 <211> LENGTH: 81 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: IL-1 ANTAGONIST Fc <400> SEQUENCE: 1119 gaataacata tgttcgaatg gaccccgggt tactggcagc cgtacgctct gccgctgggt 60 ggaggcggtg gggacaaaac t 81<210> SEQ ID NO 1120 <211> LENGTH: 48 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc VEGF ANTAGONIST <400> SEQUENCE: 1120 atttgattct agaaggagga ataacatatg gacaaaactc acacatgt 48 <210> SEQ ID NO 1121 <211> LENGTH: 51 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc VEGF ANTAGONIST <400> SEQUENCE: 1121 gtcacagttc ggttcaacac caccaccacc acctttaccc ggagacaggg a 51 <210> SEQ ID NO 1122 <211> LENGTH: 54 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc VEGF ANTAGONIST <400> SEQUENCE: 1122 tccctgtctc cgggtaaagg tggtggtggt ggtgttgaac cgaactgtga catc 54 <210> SEQ ID NO 1123 <211> LENGTH: 39 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Fc VEGF ANTAGONIST <400> SEQUENCE: 1123 ccgcggatcc tcgagttaca gacgttcaaa acattccca 39 <210> SEQ ID NO 1124 <211> LENGTH: 48 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF ANTAGONIST Fc <400> SEQUENCE: 1124 atttgattct agaaggagga ataacatatg gttgaaccga actgtgac 48 <210> SEQ ID NO 1125 <211> LENGTH: 51 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF ANTAGONIST Fc <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2)..(2) <223> OTHER INFORMATION: Position 2, Xaa is L-lys, D-lys, or an ornithylresidue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (3)..(3) <223> OTHER INFORMATION: Position 3, Xaa is L-tyr, D-ytr, phe, trp, or ap-aminophenylalanyl residue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, Xaa is a hydropholic aliphaticamino acid residue <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4)..(4) <223> OTHER INFORMATION: Position 4, optional attachment to leu,norleucyl, D-ala, Asn-Ser, asn-ser-ile, asn-ser-tyr, asn-ser-ile-leu, asn-ser-tyr-leu, or asn-ser-tyr-leu-asn <400> SEQUENCE: 1125 acatgtgtga gttttgtcac caccaccacc acccagacgt tcaaaacatt c 51 <210> SEQ ID NO 1126 <211> LENGTH: 51 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF ANTAGONIST Fc <400> SEQUENCE: 1126 gaatgttttg aacgtctggg tggtggtggt ggtgacaaaa ctcacacatg t 51 <210> SEQ ID NO 1127 <211> LENGTH: 39 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: VEGF ANTAGONIST Fc <400> SEQUENCE: 1127 ccgcggatcc tcgagttatt tacccggaga cagggagag 39 <210> SEQ ID NO 1128 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SYNTHETIC SCHEME FOR PREPARATION OF PEGYLATED PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Butoxycarbonyl group attached to the amino terminus. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 5, 24 and)..(27) <223> OTHER INFORMATION: Tert-butyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7, 13, 29 and)..(35) <223> OTHER INFORMATION: 2,2,4,6,7-pendamethyldihydrobenzofuran-5-sulfonyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8 and)..(30) <223> OTHER INFORMATION: Trityl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9 and)..(31) <223> OTHER INFORMATION: Butoxycarbonyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18)..(18) <223> OTHER INFORMATION: 1-(4,4-dimethyl-2,6-dioxo-cyclohexylidene)ethyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (36)..(36) <223> OTHER INFORMATION: Methoxy resin attached to the carboxyl terminus. <400> SEQUENCE: 1128 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Lys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 1129 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SYNTHETIC SCHEME FOR PREPARATION OF PEGYLATED PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Butoxycarbonyl group attached to the amino terminus. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 5, 24 and)..(27) <223> OTHER INFORMATION: Tert-butyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7, 12, 29 and)..(35) <223> OTHER INFORMATION: 2,2,4,6,7-pendamethyldihydrobenzofuran-5-sulfonyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8 and)..(30) <223> OTHER INFORMATION: Trityl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9 and)..(31) <223> OTHER INFORMATION: Butoxycarbonyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (36)..(36) <223> OTHER INFORMATION: Methoxy resin attached to the carboxyl terminus. <400> SEQUENCE: 1129 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Lys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 1130 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SYNTHETIC SCHEME FOR PREPARATION OF PEGYLATED PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(1) <223> OTHER INFORMATION: Butoxycarbonyl group attached to the amino terminus. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 5, 24 and)..(27) <223> OTHER INFORMATION: Tert-butyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7, 13, 29 and)..(35) <223> OTHER INFORMATION: 2,2,4,6,7-pendamethyldihydrobenzofuran-5-sulfonyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8 and)..(30) <223> OTHER INFORMATION: Trityl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9 and)..(31) <223> OTHER INFORMATION: Butoxycarbonyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18)..(18) <223> OTHER INFORMATION: Bromoacetyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (36)..(36) <223> OTHER INFORMATION: Methoxy resin attached to the carboxyl terminus. <400> SEQUENCE: 1130 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Lys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 1131 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SYNTHETIC SCHEME FOR PREPARATION OF PEGYLATED PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18)..(18) <223> OTHER INFORMATION: Bromoacetyl group attached to the sidechain. <400> SEQUENCE: 1131 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Lys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 1132 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SYNTHETIC SCHEME FOR PREPARATION OF PEGYLATED PEPTIDE <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2, 5, 24 and)..(27) <223> OTHER INFORMATION: Tert-butyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (7, 13, 29 and)..(35) <223> OTHER INFORMATION: 2,2,4,6,7-pendamethyldihydrobenzofuran-5-sulfonyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (8, 18 and)..(30) <223> OTHER INFORMATION: Trityl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (9 and)..(31) <223> OTHER INFORMATION: Butoxycarbonyl group attached to the sidechain. <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (36)..(36) <223> OTHER INFORMATION: Methoxy resin attached to the carboxyl terminus. <400> SEQUENCE: 1132 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Cys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35 <210> SEQ ID NO 1133 <211> LENGTH: 36 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: SYNTHETIC SCHEME FOR PREPARATION OF PEGYLATED PEPTIDE <400> SEQUENCE: 1133 Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu Ala Ala Arg Ala Gly Gly 1 5 10 15 Gly Cys Gly Gly Gly Gly Ile Glu Gly Pro Thr Leu Arg Gln Trp Leu 20 25 30 Ala Ala Arg Ala 35
Claims (51)
1. A composition of matter of the formula
(X1)a-F1-(X2)b
and multimers thereof, wherein:
F1 is an Fc domain;
X1 and X2 are each independently selected from -(L1)c-P1, -(L1)c-P1-(L2)d-P2, (L1)c-P1-(L2)d-P2-(L3)e-P1, and -(L1)c-P-(L2)d-P2-(L1)e-P1-(L4)f-P4
P1, P2, P1, and P4 are each independently sequences of pharmacologically active peptides;
L1, L2, L3, and L4 are each independently linkers; and
a, b, c, d, e, and f are each independently 0 or 1, provided that at least one of a and b is 1.
2. The composition of matter of claim 1 of the formulae
X1-F1
or
F1-X2.
3. The composition of matter of claim 1 of the formula
F1-(L1)c-P1.
4. The composition of matter of claim 1 of the formula
F1-(L1)c-P1-(L2)d-P2.
5. The composition of matter of claim 1 wherein F1 is an IgG Fc domain.
6. The composition of matter of claim 1 wherein F1 is an IgG1 Fc domain.
7. The composition of matter of claim 1 wherein F1 comprises the sequence of SEQ ID NO: 2.
8. The composition of matter of claim 1 wherein X1 and X2 comprise an IL-1 antagonist peptide sequence.
9. The composition of matter of claim 8 wherein the IL-1 antagonist peptide sequence is selected from SEQ ID NOS: 212, 907, 908, 909, 910, 917, and 979.
10. The composition of matter of claim 8 wherein the IL-1 antagonist peptide sequence is selected from SEQ ID NOS: 213 to 271, 671 to 906, 911 to 916, and 918 to 1023.
11. The composition of matter of claim 8 wherein F1 comprises the sequence of SEQ ID NO: 2.
12. The composition of matter of claim 1 wherein X1 and X2 comprise an EPO-mimetic peptide sequence.
13. The composition of matter of claim 12 wherein the EPO-mimetic peptide sequence is selected from Table 5.
14. The composition of matter of claim 12 wherein F1 comprises the sequence of SEQ ID NO: 2.
15. The composition of matter of claim 12 comprising a sequence selected from SEQ ID NOS: 83, 84, 85, 124, 419, 420, 421, and 461.
16. The composition of matter of claim 12 comprising a sequence selected from SEQ ID NOS: 339 and 340.
17. The composition of matter of claim 12 comprising a sequence selected from SEQ ID NOS: 20 and 22.
18. The composition of matter of claim 3 wherein P1 is a TPO-mimetic peptide sequence.
19. The composition of matter of claim 18 wherein P1 is a TPO-mimetic peptide sequence selected from Table 6.
20. The composition of matter of claim 18 wherein F1 comprises the sequence of SEQ ID NO: 2.
21. The composition of matter of claim 18 having a sequence selected from SEQ ID NOS: 6 and 12.
22. A DNA encoding a composition of matter of any of claims 1 to 21 .
23. An expression vector comprising the DNA of claim 22 .
24. A host cell comprising the expression vector of claim 23 .
25. The cell of claim 24 , wherein the cell is an E. coli cell.
26. A process for preparing a pharmacologically active compound, which comprises
a) selecting at least one randomized peptide that modulates the activity of a protein of interest; and
b) preparing a pharmacologic agent comprising at least one Fc domain covalently linked to at least one amino acid sequence of the selected peptide or peptides.
27. The process of claim 26 , wherein the peptide is selected in a process comprising screening of a phage display library, an E. coli display library, a ribosomal library, or a chemical peptide library.
28. The process of claim 26 , wherein the preparation of the pharmacologic agent is carried out by:
a) preparing a gene construct comprising a nucleic acid sequence encoding the selected peptide and a nucleic acid sequence encoding an Fc domain; and
b) expressing the gene construct.
29. The process of claim 26 , wherein the gene construct is expressed in an E. coli cell.
30. The process of claim 26 , wherein the protein of interest is a cell surface receptor.
31. The process of claim 26 , wherein the protein of interest has a linear epitope.
32. The process of claim 26 , wherein the protein of interest is a cytokine receptor.
33. The process of claim 26 , wherein the peptide is an EPO-mimetic peptide.
34. The process of claim 26 , wherein the peptide is a TPO-mimetic peptide.
35. The process of claim 26 , wherein the peptide is an IL-1 antagonist peptide.
36. The process of claim 26 , wherein the peptide is an MMP inhibitor peptide or a VEGF antagonist peptide.
37. The process of claim 26 , wherein the peptide is a TNF-antagonist peptide.
38. The process of claim 26 , wherein the peptide is a CTLA4-mimetic peptide.
39. The process of claim 26 , wherein the peptide is selected from Tables 4 to 20.
40. The process of claim 26 , wherein the selection of the peptide is carried out by a process comprising:
a) preparing a gene construct comprising a nucleic acid sequence encoding a first selected peptide and a nucleic acid sequence encoding an Fc domain;
b) conducting a polymerase chain reaction using the gene construct and mutagenic primers, wherein
i) a first mutagenic primer comprises a nucleic acid sequence complementary to a sequence at or near the 5′ end of a coding strand of the gene construct, and
ii) a second mutagenic primer comprises a nucleic acid sequence complementary to the 3′ end of the noncoding strand of the gene construct.
41. The process of claim 26 , wherein the compound is derivatized.
42. The process of claim 26 , wherein the derivatized compound comprises a cyclic portion, a cross-linking site, a non-peptidyl linkage, an N-terminal replacement, a C-terminal replacement, or a modified amino acid moiety.
43. The process of claim 26 wherein the Fc domain is an IgG Fc domain.
44. The process of claim 26 , wherein the vehicle is an IgG1 Fc domain.
45. The process of claim 26 , wherein the vehicle comprises the sequence of SEQ ID NO: 2.
46. The process of claim 26 , wherein the compound prepared is of the formula
(X1)a-F1-(X2)b
and multimers thereof, wherein:
F1 is an Fc domain;
X1 and X2 are each independently selected from -(L1)c-P1, -(L1)c-P1-(L2)d-P2, -(L1)c-P1-(L2)d-P2(L3)e-P3, and -(L1)c-P1-(L2)d-P2-(L3)e-P3-(L4)f-P4
P1, P2, P3, and P4 are each independently sequences of pharmacologically active peptides;
L1, L2, L3, and L4 are each independently linkers; and
a, b, c, d, e, and f are each independently 0 or 1, provided that at least one of a and b is 1.
47. The process of claim 46 , wherein the compound prepared is of the formulae
X1-F1
or
F1-X2.
48. The process of claim 46 , wherein the compound prepared is of the formulae
F1-(L1)c-P1
or
F1-(L1)c-P1-(L2)d-P2.
49. The process of claim 46 , wherein F1 is an IgG Fc domain.
50. The process of claim 46 , wherein F1 is an IgG1 Fc domain.
51. The process of claim 46 , wherein F1 comprises the sequence of SEQ ID NO: 2.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/645,761 US20040071712A1 (en) | 1998-10-23 | 2003-08-18 | Modified peptides as therapeutic agents |
US11/591,002 US20070049532A1 (en) | 1998-10-23 | 2006-10-31 | Modified peptides as therapeutic agents |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10537198P | 1998-10-23 | 1998-10-23 | |
US09/428,082 US6660843B1 (en) | 1998-10-23 | 1999-10-22 | Modified peptides as therapeutic agents |
US10/645,761 US20040071712A1 (en) | 1998-10-23 | 2003-08-18 | Modified peptides as therapeutic agents |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/428,082 Continuation US6660843B1 (en) | 1998-10-23 | 1999-10-22 | Modified peptides as therapeutic agents |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/591,002 Division US20070049532A1 (en) | 1998-10-23 | 2006-10-31 | Modified peptides as therapeutic agents |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040071712A1 true US20040071712A1 (en) | 2004-04-15 |
Family
ID=26802505
Family Applications (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/428,082 Expired - Lifetime US6660843B1 (en) | 1998-10-23 | 1999-10-22 | Modified peptides as therapeutic agents |
US10/609,217 Expired - Fee Related US7166707B2 (en) | 1998-10-23 | 2003-06-27 | Modified peptides as therapeutic agents |
US10/632,388 Expired - Lifetime US7189827B2 (en) | 1998-10-23 | 2003-07-31 | Modified peptides as therapeutic agents |
US10/645,761 Abandoned US20040071712A1 (en) | 1998-10-23 | 2003-08-18 | Modified peptides as therapeutic agents |
US10/653,048 Expired - Fee Related US7186810B2 (en) | 1998-10-23 | 2003-08-29 | Modified peptides as therapeutic agents |
US10/651,723 Expired - Fee Related US7169905B2 (en) | 1998-10-23 | 2003-08-29 | Modified peptides as therapeutic agents |
US11/591,002 Abandoned US20070049532A1 (en) | 1998-10-23 | 2006-10-31 | Modified peptides as therapeutic agents |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/428,082 Expired - Lifetime US6660843B1 (en) | 1998-10-23 | 1999-10-22 | Modified peptides as therapeutic agents |
US10/609,217 Expired - Fee Related US7166707B2 (en) | 1998-10-23 | 2003-06-27 | Modified peptides as therapeutic agents |
US10/632,388 Expired - Lifetime US7189827B2 (en) | 1998-10-23 | 2003-07-31 | Modified peptides as therapeutic agents |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/653,048 Expired - Fee Related US7186810B2 (en) | 1998-10-23 | 2003-08-29 | Modified peptides as therapeutic agents |
US10/651,723 Expired - Fee Related US7169905B2 (en) | 1998-10-23 | 2003-08-29 | Modified peptides as therapeutic agents |
US11/591,002 Abandoned US20070049532A1 (en) | 1998-10-23 | 2006-10-31 | Modified peptides as therapeutic agents |
Country Status (29)
Country | Link |
---|---|
US (7) | US6660843B1 (en) |
EP (1) | EP1144454B2 (en) |
JP (9) | JP2003512011A (en) |
KR (3) | KR100753305B1 (en) |
CN (8) | CN1781946A (en) |
AT (1) | ATE380828T1 (en) |
AU (3) | AU767725B2 (en) |
BG (1) | BG65721B1 (en) |
BR (1) | BR9914708A (en) |
CA (1) | CA2347131C (en) |
CY (1) | CY1107881T1 (en) |
CZ (1) | CZ304242B6 (en) |
DE (1) | DE69937752T3 (en) |
DK (1) | DK1144454T4 (en) |
EA (1) | EA005404B1 (en) |
ES (1) | ES2299278T5 (en) |
HK (2) | HK1042097B (en) |
HU (1) | HU229485B1 (en) |
IL (2) | IL142365A0 (en) |
MX (1) | MXPA01003873A (en) |
NO (1) | NO331733B1 (en) |
NZ (2) | NZ510888A (en) |
PL (1) | PL211164B1 (en) |
PT (1) | PT1144454E (en) |
RS (1) | RS51852B (en) |
SI (1) | SI1144454T2 (en) |
SK (1) | SK287037B6 (en) |
WO (1) | WO2000024782A2 (en) |
ZA (1) | ZA200102753B (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070134234A1 (en) * | 2005-09-29 | 2007-06-14 | Viral Logic Systems Technology Corp. | Immunomodulatory compositions and uses therefor |
US20080131431A1 (en) * | 2006-05-15 | 2008-06-05 | Viral Logic Systems Technology Corp. | CD47 related compositions and methods for treating immunological diseases and disorders |
US20090202619A1 (en) * | 2005-02-18 | 2009-08-13 | The University Of Tokushima | Polyoxyalkylene chain-containing lipid derivative and lipid film structure containing such derivative |
US20100239579A1 (en) * | 2006-05-15 | 2010-09-23 | Viral Logic Systems Technology Corp. | CD47 Related Compositions and Methods for Treating Immunological Diseases and Disorders |
EP2275816A2 (en) | 2006-03-22 | 2011-01-19 | Viral Logic Systems Technology Corp. | Methods for identifying polypeptide targets and uses thereof for treating immunological diseases |
WO2015057820A3 (en) * | 2013-10-15 | 2015-06-18 | Roberts S Kenny | Peptide constructs and well-defined aggregates thereof |
US9283260B2 (en) | 2006-04-21 | 2016-03-15 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
Families Citing this family (541)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6743777B1 (en) * | 1992-03-19 | 2004-06-01 | Eli Lilly And Company | Cyclic peptide antifungal agents and process for preparation thereof |
US7091311B2 (en) * | 1996-06-07 | 2006-08-15 | Smithkline Beecham Corporation | Peptides and compounds that bind to a receptor |
KR100719202B1 (en) | 1998-10-23 | 2007-05-16 | 키린-암젠 인코포레이티드 | A COMPOUND BINDING TO MPl RECEPTOR AND A PHARMACEUTICAL COMPOSITION THEREOF |
US7488590B2 (en) | 1998-10-23 | 2009-02-10 | Amgen Inc. | Modified peptides as therapeutic agents |
US6660843B1 (en) * | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
WO2000047740A2 (en) * | 1999-02-12 | 2000-08-17 | Amgen Inc. | Tnf-related proteins |
DK1157030T3 (en) | 1999-03-03 | 2003-12-22 | Lilly Co Eli | Enchinocanidin / carbohydrate complexes |
ATE294571T1 (en) * | 1999-03-03 | 2005-05-15 | Lilly Co Eli | ECHINOCANDIN PHARMACEUTICAL COMPOSITIONS |
ATE330967T1 (en) | 1999-07-02 | 2006-07-15 | Genentech Inc | PEPTIDE COMPOUNDS BINDING TO HER2 |
IL147269A0 (en) | 1999-07-02 | 2002-08-14 | Genentech Inc | FVIIa ANTAGONISTS |
JP4944324B2 (en) * | 1999-07-13 | 2012-05-30 | ボルダー バイオテクノロジー, インコーポレイテッド | Immunoglobulin fusion protein |
SK782002A3 (en) | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
EP1274723A4 (en) * | 1999-07-29 | 2003-10-01 | Univ Johns Hopkins | ACTIVATION OF PEPTIDE PRODRUGS BY hK2 |
US7459540B1 (en) | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
US6808902B1 (en) * | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
DK1290013T3 (en) * | 2000-04-21 | 2006-06-26 | Amgen Inc | Apo-A1 / All-peptide derivatives |
EP1278778A2 (en) * | 2000-05-03 | 2003-01-29 | Amgen Inc., | Modified peptides, comprising an fc domain, as therapeutic agents |
US20020090646A1 (en) * | 2000-05-03 | 2002-07-11 | Amgen Inc. | Calcitonin-related molecules |
AU2001261557B2 (en) | 2000-05-12 | 2005-06-30 | Amgen Inc. | Methods and compositions of matter concerning april/g70, bcma, blys/agp-3, and taci |
US7259146B2 (en) | 2000-05-26 | 2007-08-21 | Ortho-Mcneil Pharmaceutical, Inc. | Neuroprotective peptides |
BR0111182A (en) * | 2000-05-26 | 2004-02-25 | Ortho Mcneil Pharm Inc | Neuroprotective Peptides |
EP1292709B1 (en) * | 2000-06-02 | 2012-01-18 | Eidgenössische Technische Hochschule Zürich | Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds |
US7355019B2 (en) * | 2000-06-06 | 2008-04-08 | Sibtech, Inc. | Cysteine-containing peptide tag for site-specific conjugation of proteins |
CA2421588C (en) * | 2000-09-05 | 2010-01-26 | Amgen Inc. | Tnf receptor-like molecules and uses thereof |
US7396917B2 (en) | 2000-12-05 | 2008-07-08 | Alexion Pharmaceuticals, Inc. | Rationally designed antibodies |
AU2003295623B2 (en) * | 2000-12-05 | 2008-06-05 | Alexion Pharmaceuticals, Inc. | Rationally designed antibodies |
CA2436671C (en) * | 2000-12-05 | 2015-02-03 | Alexion Pharmaceuticals, Inc. | Rationally designed antibodies |
US20040253242A1 (en) * | 2000-12-05 | 2004-12-16 | Bowdish Katherine S. | Rationally designed antibodies |
US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
US7829084B2 (en) * | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
US7491702B2 (en) * | 2001-04-18 | 2009-02-17 | The Open University | Polypeptides related to amyloid precursor protein, pharmaceutical compositions thereof, and methods of treatment using the same |
US7622446B2 (en) * | 2001-04-18 | 2009-11-24 | The Open University | Polypeptides, derivatives and uses thereof |
BR0209546A (en) | 2001-05-11 | 2004-06-29 | Amgen Inc | Composition of matter, DNA, expression vector, host cell, and methods for treating B-cell mediated autoimmune disease, lupus, B-cell mediated cancer, and B-cell lymphoma |
TR201809008T4 (en) * | 2001-06-26 | 2018-07-23 | Amgen Fremont Inc | Antibodies against opgl. |
AU2002340118B2 (en) | 2001-10-04 | 2007-09-13 | Immunex Corporation | UL16 Binding protein 4 |
US7332474B2 (en) * | 2001-10-11 | 2008-02-19 | Amgen Inc. | Peptides and related compounds having thrombopoietic activity |
US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
US7521053B2 (en) | 2001-10-11 | 2009-04-21 | Amgen Inc. | Angiopoietin-2 specific binding agents |
MX339524B (en) * | 2001-10-11 | 2016-05-30 | Wyeth Corp | Novel immunogenic compositions for the prevention and treatment of meningococcal disease. |
US7205275B2 (en) | 2001-10-11 | 2007-04-17 | Amgen Inc. | Methods of treatment using specific binding agents of human angiopoietin-2 |
US7737260B2 (en) | 2003-11-13 | 2010-06-15 | Hanmi Pharm. Co., Ltd | Protein complex using an immunoglobulin fragment and method for the preparation thereof |
US20030113270A1 (en) * | 2001-12-14 | 2003-06-19 | Clark Abbot F. | Vasoactive intestinal peptides for glaucomatous retinopathy |
US7056535B2 (en) * | 2001-12-20 | 2006-06-06 | Kimberly-Clark Worldwide, Inc. | Triggered release from proteinoid microspheres |
US20030138975A1 (en) * | 2001-12-20 | 2003-07-24 | Kimberly-Clark Worldwide, Inc. | Diagnostic signal amplification with proteinoid microspheres |
US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
US8188231B2 (en) | 2002-09-27 | 2012-05-29 | Xencor, Inc. | Optimized FC variants |
US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
US7662925B2 (en) | 2002-03-01 | 2010-02-16 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
DE10209821A1 (en) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Coupling of proteins to a modified polysaccharide |
DE10209822A1 (en) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Coupling of low molecular weight substances to a modified polysaccharide |
JP2005521401A (en) | 2002-03-27 | 2005-07-21 | イミュネックス・コーポレーション | Methods for increasing polypeptide production |
US20030191056A1 (en) | 2002-04-04 | 2003-10-09 | Kenneth Walker | Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins |
PL375041A1 (en) | 2002-04-05 | 2005-11-14 | Amgen Inc. | Human anti-opgl neutralizing antibodies as selective opgl pathway inhibitors |
US6991800B2 (en) * | 2002-06-13 | 2006-01-31 | Vicuron Pharmaceuticals Inc. | Antifungal parenteral products |
WO2004002417A2 (en) * | 2002-06-28 | 2004-01-08 | Centocor, Inc. | Mammalian ch1 deleted mimetibodies, compositions, methods and uses |
DE50212514D1 (en) * | 2002-08-06 | 2008-08-28 | Aplagen Gmbh | Synthetic mimetics of physiological binding molecules |
JP4667868B2 (en) * | 2002-08-06 | 2011-04-13 | アプラーゲン ゲゼルシャフト ミット ベシュレンクテル ハフツング | Binding molecule |
WO2004019866A2 (en) | 2002-08-28 | 2004-03-11 | Immunex Corporation | Compositions and methods for treating cardiovascular disease |
BRPI0314038B8 (en) | 2002-09-06 | 2021-05-25 | Amgen Inc | isolated human antibody, isolated nucleic acid molecule, vector, use of an antibody, and pharmaceutical composition |
PL217085B1 (en) * | 2002-09-11 | 2014-06-30 | Fresenius Kabi Gmbh | Hasylated polypeptides, especially hasylated erythropoietin |
ES2781475T3 (en) | 2002-09-18 | 2020-09-02 | Janssen Pharmaceuticals Inc | Methods to increase the production of hematopoietic stem cells and platelets |
US6919426B2 (en) | 2002-09-19 | 2005-07-19 | Amgen Inc. | Peptides and related molecules that modulate nerve growth factor activity |
BRPI0314814C1 (en) | 2002-09-27 | 2021-07-27 | Xencor Inc | antibody comprising an fc variant |
US20040149235A1 (en) * | 2002-10-04 | 2004-08-05 | Pogue Albert S. | Apparatus and method for removal of waste from animal production facilities |
NZ570811A (en) | 2002-11-09 | 2009-11-27 | Immunocore Ltd | T cell receptor display |
AR042545A1 (en) * | 2002-12-20 | 2005-06-22 | Amgen Inc | BINDING AGENTS THAT INHIBIT MIOSTATINE |
US7125849B2 (en) * | 2003-01-14 | 2006-10-24 | The Scripps Research Institute | Peptide-based angiogenesis inhibitors and methods of use thereof |
DE10303974A1 (en) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid β (1-42) oligomers, process for their preparation and their use |
DE502004007051D1 (en) * | 2003-02-06 | 2008-06-19 | Merck Patent Gmbh | PEPTIDIC SULFONAMIDE |
US8084582B2 (en) | 2003-03-03 | 2011-12-27 | Xencor, Inc. | Optimized anti-CD20 monoclonal antibodies having Fc variants |
US20090010920A1 (en) | 2003-03-03 | 2009-01-08 | Xencor, Inc. | Fc Variants Having Decreased Affinity for FcyRIIb |
US8388955B2 (en) | 2003-03-03 | 2013-03-05 | Xencor, Inc. | Fc variants |
US9051373B2 (en) | 2003-05-02 | 2015-06-09 | Xencor, Inc. | Optimized Fc variants |
US7348004B2 (en) * | 2003-05-06 | 2008-03-25 | Syntonix Pharmaceuticals, Inc. | Immunoglobulin chimeric monomer-dimer hybrids |
US20050281829A1 (en) * | 2003-05-06 | 2005-12-22 | Hehir Cristina A T | Fc chimeric proteins with anti-HIV drugs |
WO2004101740A2 (en) | 2003-05-06 | 2004-11-25 | Syntonix Pharmaceuticals, Inc. | Clotting factor-fc chimeric proteins to treat hemophilia |
WO2004100882A2 (en) * | 2003-05-06 | 2004-11-25 | Syntonix Pharmaceuticals, Inc. | Inhibition of drug binding to serum albumin |
TWI353991B (en) * | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
DE602004020610D1 (en) | 2003-05-12 | 2009-05-28 | Affymax Inc | NEW PEPTIDE BINDING TO THE ERYTHROPOIETIN RECEPTOR |
MXPA05012315A (en) * | 2003-05-12 | 2006-04-18 | Affymax Inc | Novel poly(ethylene glycol) modified compounds and uses thereof. |
CN1823088B (en) * | 2003-05-12 | 2011-04-13 | 阿费麦克斯公司 | Novel peptides that bind to the erythropoietin receptor |
EP2204193A3 (en) * | 2003-05-12 | 2010-08-18 | Affymax, Inc. | Novel spacer moiety for poly(ethylene glycol)-modified peptide-based compounds |
JP4866238B2 (en) * | 2003-06-20 | 2012-02-01 | シーメンス・ヘルスケア・ダイアグノスティックス・プロダクツ・ゲーエムベーハー | Novel surface protein (HBsAg) variant of hepatitis B virus |
EP1648998B1 (en) | 2003-07-18 | 2014-10-01 | Amgen Inc. | Specific binding agents to hepatocyte growth factor |
CA2533512C (en) | 2003-07-25 | 2013-06-11 | Amgen Inc. | Antagonists and agonists of ldcam and methods of use |
WO2005014655A2 (en) * | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
DE602004023956D1 (en) | 2003-08-18 | 2009-12-17 | Univ California | POLYPEPTIDE DISPLAY LIBRARIES AND METHOD FOR THE PRODUCTION AND USE THEREOF |
US8158589B2 (en) | 2003-08-22 | 2012-04-17 | Proyecto Biomedicine Cima, S.L. | Peptides with the capacity to bind to transforming growth factor β1 (TGF-β1) |
ES2304069B1 (en) * | 2003-08-22 | 2009-08-12 | Proyecto De Biomedicina Cima, S.L. | PEPTIDES ABLE TO JOIN THE TRANSFORMING FACTOR OF BETA 1 GROWTH (TGF-B1). |
US8101720B2 (en) | 2004-10-21 | 2012-01-24 | Xencor, Inc. | Immunoglobulin insertions, deletions and substitutions |
US9714282B2 (en) | 2003-09-26 | 2017-07-25 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
UA89481C2 (en) * | 2003-09-30 | 2010-02-10 | Центокор, Инк. | Human epo mimetic hinge core mimetibodies, compositions, methods and uses |
CN1890383A (en) * | 2003-09-30 | 2007-01-03 | 森托科尔公司 | Hinge core mimetibodies, compositions, methods and uses |
EP1684791A4 (en) | 2003-10-27 | 2009-07-01 | Amgen Inc | Compositions and methods to modulate an immune response to an immunogenic therapeutic agent |
US8110665B2 (en) | 2003-11-13 | 2012-02-07 | Hanmi Holdings Co., Ltd. | Pharmaceutical composition comprising an immunoglobulin FC region as a carrier |
JP4982183B2 (en) | 2003-12-12 | 2012-07-25 | ジェネンコー・インターナショナル・インク | CAB molecule |
EP1709072A1 (en) * | 2004-01-29 | 2006-10-11 | Genentech, Inc. | Variants of the extracellular domain of bcma and uses thereof |
WO2005092391A2 (en) * | 2004-03-11 | 2005-10-06 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
DE202005021885U1 (en) | 2004-03-11 | 2011-03-03 | Fresenius Kabi Deutschland Gmbh | Hydroxyalkyl starch-protein conjugates prepared by reductive amination |
TR201816556T4 (en) * | 2004-04-02 | 2018-11-21 | Swedish Orphan Biovitrum Ab Publ | METHODS FOR REDUCING IL-1RA AGGREGATION |
US20050222040A1 (en) * | 2004-04-05 | 2005-10-06 | Blm Group, Inc. | Vertebrate peptide modulators of lipid metabolism |
ATE478894T1 (en) | 2004-04-15 | 2010-09-15 | Genencor Int | ANTI-CEA SCFV-BETA-LACTAMASE CONSTRUCTS (CAB MOLECULES) IN ADEPT |
JP2005309295A (en) * | 2004-04-26 | 2005-11-04 | Nec Corp | Element, device, and system for optical amplification |
US20050281740A1 (en) * | 2004-06-16 | 2005-12-22 | Glen Gong | Imaging damaged lung tissue |
US20050281799A1 (en) * | 2004-06-16 | 2005-12-22 | Glen Gong | Targeting damaged lung tissue using compositions |
US20050281798A1 (en) * | 2004-06-16 | 2005-12-22 | Glen Gong | Targeting sites of damaged lung tissue using composition |
US7553810B2 (en) * | 2004-06-16 | 2009-06-30 | Pneumrx, Inc. | Lung volume reduction using glue composition |
US20050281739A1 (en) * | 2004-06-16 | 2005-12-22 | Glen Gong | Imaging damaged lung tissue using compositions |
US7608579B2 (en) * | 2004-06-16 | 2009-10-27 | Pneumrx, Inc. | Lung volume reduction using glue compositions |
US7678767B2 (en) | 2004-06-16 | 2010-03-16 | Pneumrx, Inc. | Glue compositions for lung volume reduction |
KR101100059B1 (en) * | 2004-06-30 | 2011-12-29 | 넥타르 테라퓨틱스 | Polymer-factor ix moiety conjugates |
WO2006014567A2 (en) | 2004-07-08 | 2006-02-09 | Pneumrx, Inc. | Pleural effusion treatment device, method and material |
US8143380B2 (en) * | 2004-07-08 | 2012-03-27 | Amgen Inc. | Therapeutic peptides |
ME00226B (en) | 2004-07-15 | 2011-02-10 | Medarex Llc | Human anti-ngf neutralizing antibodies as selective ngf pathway inhibitors |
US20150010550A1 (en) | 2004-07-15 | 2015-01-08 | Xencor, Inc. | OPTIMIZED Fc VARIANTS |
WO2007001332A2 (en) * | 2004-08-04 | 2007-01-04 | University Of Massachusetts | Anti-pathogen immunoadhesins |
US20060210542A1 (en) * | 2004-08-16 | 2006-09-21 | Yurkow Edward J | Use of TPO mimetic compounds and pharmaceutical compositions in the treatment of anemia |
US7393662B2 (en) * | 2004-09-03 | 2008-07-01 | Centocor, Inc. | Human EPO mimetic hinge core mimetibodies, compositions, methods and uses |
AU2005289685B2 (en) | 2004-09-24 | 2009-07-16 | Amgen Inc. | Modified Fc molecules |
WO2006036922A2 (en) * | 2004-09-27 | 2006-04-06 | Centocor, Inc. | Srage mimetibody, compositions, methods and uses |
WO2006052493A1 (en) * | 2004-11-04 | 2006-05-18 | Genentech, Inc. | Polypeptides that bind baff and/or april |
WO2006062685A2 (en) * | 2004-11-11 | 2006-06-15 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
WO2006060148A2 (en) * | 2004-11-11 | 2006-06-08 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
DK2325207T3 (en) | 2004-11-12 | 2017-06-06 | Xencor Inc | Fc variants with altered binding to FcRn |
US8546543B2 (en) | 2004-11-12 | 2013-10-01 | Xencor, Inc. | Fc variants that extend antibody half-life |
US8802820B2 (en) | 2004-11-12 | 2014-08-12 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US20070110760A1 (en) * | 2005-01-14 | 2007-05-17 | Monroe John G | Methods and compositions targeting viral and cellular ITAM motifs, and use of same in identifying compounds with therapeutic activity |
US8053415B2 (en) * | 2005-01-21 | 2011-11-08 | Washington University In St. Louis | Compounds having RD targeting motifs |
US7723472B2 (en) * | 2005-02-28 | 2010-05-25 | The Regents Of The University Of California | Extracellular matrix binding chimeric proteins and methods of use thereof |
US20060241040A1 (en) * | 2005-04-06 | 2006-10-26 | Alberto Visintin | Methods of treating disorders associated with toll-like receptor 4 (TLR4) signalling |
US7833979B2 (en) * | 2005-04-22 | 2010-11-16 | Amgen Inc. | Toxin peptide therapeutic agents |
DK1877102T3 (en) | 2005-04-28 | 2014-07-21 | Danisco Us Inc | TAB MOLECULES |
US8324159B2 (en) * | 2005-06-03 | 2012-12-04 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
US7550433B2 (en) | 2005-06-03 | 2009-06-23 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
US7919461B2 (en) | 2005-06-03 | 2011-04-05 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
SG162788A1 (en) | 2005-06-14 | 2010-07-29 | Amgen Inc | Self-buffering protein formulations |
CA2648732A1 (en) * | 2005-06-23 | 2006-12-28 | Aplagen Gmbh | Supravalent compounds |
US7566456B2 (en) * | 2005-06-23 | 2009-07-28 | Haiming Chen | Allergen vaccine proteins for the treatment and prevention of allergic diseases |
US7700739B2 (en) * | 2005-06-30 | 2010-04-20 | Abbott Laboratories | IL-12/p40 binding proteins |
CA2614972C (en) | 2005-07-18 | 2014-08-19 | Amgen Inc. | Human anti-b7rp1 neutralizing antibodies |
PL1912675T3 (en) * | 2005-07-25 | 2014-10-31 | Emergent Product Dev Seattle | B-cell reduction using cd37-specific and cd20-specific binding molecules |
WO2007037795A2 (en) | 2005-08-05 | 2007-04-05 | Amgen Inc. | Stable aqueous protein or antibody pharmaceutical formulations and their preparation |
US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
WO2007021129A1 (en) * | 2005-08-16 | 2007-02-22 | Hanmi Pharmaceutical Co., Ltd. | A method for the mass production of immunoglobulin fc region deleted initial methionine residues |
US20090215992A1 (en) * | 2005-08-19 | 2009-08-27 | Chengbin Wu | Dual variable domain immunoglobulin and uses thereof |
US7612181B2 (en) * | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
EP1919931A4 (en) | 2005-08-31 | 2010-01-20 | Univ California | Cellular libraries of peptide sequences (clips) and methods of using the same |
KR100780405B1 (en) * | 2005-08-31 | 2007-11-28 | 재단법인서울대학교산학협력재단 | A Process for screening of a binding peptides specific for specific RNA and RNA binding peptides therefrom |
EP1762250A1 (en) * | 2005-09-12 | 2007-03-14 | Fresenius Kabi Deutschland GmbH | Conjugates of hydroxyalkyl starch and an active substance, prepared by chemical ligation via thiazolidine |
ES2542501T3 (en) | 2005-09-30 | 2015-08-06 | Abbvie Deutschland Gmbh & Co Kg | Protein binding domains of the protein family of repulsive targeting molecules (RGM) and functional fragments thereof, as well as their use |
CA2624189A1 (en) | 2005-10-03 | 2007-04-12 | Xencor, Inc. | Fc variants with optimized fc receptor binding properties |
JP4860703B2 (en) | 2005-10-06 | 2012-01-25 | ゼンコー・インコーポレイテッド | Optimized anti-CD30 antibody |
JP5905184B2 (en) | 2005-10-13 | 2016-04-20 | ヒューマン ジノーム サイエンシーズ, インコーポレイテッドHuman Genome Sciences, Inc. | Methods and compositions for use in treating patients with autoantibody positive disease |
US8445642B1 (en) * | 2005-10-13 | 2013-05-21 | The United States Of America As Represented By The Secretary Of Agriculture | Methods to differentiate protein conformers |
US8168592B2 (en) | 2005-10-21 | 2012-05-01 | Amgen Inc. | CGRP peptide antagonists and conjugates |
JP2009514508A (en) * | 2005-10-24 | 2009-04-09 | セントカー・インコーポレーテツド | GLP-2 mimetibodies, polypeptides, compositions, methods and uses |
ES2618785T3 (en) * | 2005-10-31 | 2017-06-22 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for treating cancer based on human FZD receptors |
US7723477B2 (en) | 2005-10-31 | 2010-05-25 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for inhibiting Wnt-dependent solid tumor cell growth |
US8067562B2 (en) | 2005-11-01 | 2011-11-29 | Amgen Inc. | Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1 |
CN102898519B (en) | 2005-11-30 | 2015-10-28 | Abbvie公司 | Monoclonal antibody of anti-amyloid beta protein and uses thereof |
EP2289909B1 (en) | 2005-11-30 | 2014-10-29 | AbbVie Inc. | Screening method, process for purifying of non-diffusible a-beta oligomers, selective antibodies against said non-diffusible a-beta oligomers and a process for manufacturing of said antibodies |
WO2007067616A2 (en) * | 2005-12-06 | 2007-06-14 | Amgen Inc | Uses of myostatin antagonists |
WO2007067564A2 (en) | 2005-12-08 | 2007-06-14 | Amgen Inc. | Improved host cells and culture methods |
KR20080077132A (en) | 2005-12-12 | 2008-08-21 | 에프. 호프만-라 로슈 아게 | Antibodies against amyloid beta 4 with glycosylated in the variable region |
US20090054763A1 (en) * | 2006-01-19 | 2009-02-26 | The Regents Of The University Of Michigan | System and method for spectroscopic photoacoustic tomography |
US9012605B2 (en) * | 2006-01-23 | 2015-04-21 | Amgen Inc. | Crystalline polypeptides |
AR059066A1 (en) | 2006-01-27 | 2008-03-12 | Amgen Inc | COMBINATIONS OF THE ANGIOPOYETINE INHIBITOR -2 (ANG2) AND THE VASCULAR ENDOTELIAL GROWTH FACTOR INHIBITOR (VEGF) |
US7625564B2 (en) * | 2006-01-27 | 2009-12-01 | Novagen Holding Corporation | Recombinant human EPO-Fc fusion proteins with prolonged half-life and enhanced erythropoietic activity in vivo |
US20070179094A1 (en) | 2006-01-31 | 2007-08-02 | Bayer Schering Pharma Ag | Modulation of MDL-1 activity for treatment of inflammatory disease |
EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
TW200745163A (en) | 2006-02-17 | 2007-12-16 | Syntonix Pharmaceuticals Inc | Peptides that block the binding of IgG to FcRn |
US8129334B2 (en) | 2006-03-31 | 2012-03-06 | The Regents Of The University Of California | Methods and compositions for treating neurodegenerative disorders and Alzheimer'S disease and improving normal memory |
WO2007115148A2 (en) * | 2006-03-31 | 2007-10-11 | Centocor, Inc. | Human mimetic epo hinge core mimetibodies |
NZ572379A (en) | 2006-04-05 | 2012-06-29 | Univ Rockefeller | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
KR101492422B1 (en) * | 2006-04-11 | 2015-02-12 | 체에스엘 베링 게엠베하 | Method of increasing the in vivo recovery of therapeutic polypeptides |
TWI395754B (en) | 2006-04-24 | 2013-05-11 | Amgen Inc | Humanized c-kit antibody |
MX363905B (en) * | 2006-06-12 | 2019-04-08 | Aptevo Res & Development Llc | Single-chain multivalent binding proteins with effector function. |
US7981425B2 (en) | 2006-06-19 | 2011-07-19 | Amgen Inc. | Thrombopoietic compounds |
CA2654661C (en) | 2006-06-26 | 2012-10-23 | Amgen Inc. | Compositions comprising modified lcat and use thereof for treating atherosclerosis |
ES2457072T3 (en) | 2006-08-14 | 2014-04-24 | Xencor, Inc. | Optimized antibodies that select as target CD19 |
HUE052220T2 (en) | 2006-09-08 | 2021-04-28 | Abbvie Bahamas Ltd | Interleukin -13 binding proteins |
CA2662549C (en) | 2006-09-08 | 2014-10-28 | Amgen Inc. | Il-1 family variants |
WO2008031009A2 (en) * | 2006-09-08 | 2008-03-13 | Genentech, Inc. | Wnt antagonists and their use in the diagnosis and treatment of wnt-mediated disorders |
US20140147441A1 (en) * | 2006-09-12 | 2014-05-29 | The General Hospital Corporation | Compositions containing alpha-1-antitrypsin and methods for use |
JP2010503687A (en) * | 2006-09-15 | 2010-02-04 | ザ バーナム インスティチュート | High affinity EphB receptor binding compounds and methods of use thereof |
KR20090071598A (en) | 2006-09-18 | 2009-07-01 | 랩터 파마슈티컬 인코포레이티드 | Treatment of liver disorders by administration of receptor-associated protein(rap)-conjugates |
CA2660795C (en) | 2006-09-18 | 2014-11-18 | Xencor, Inc. | Optimized antibodies that target hm1.24 |
WO2008036763A2 (en) * | 2006-09-20 | 2008-03-27 | Pneumrx, Inc. | Tissue adhesive compositions and methods thereof |
US20100034194A1 (en) * | 2006-10-11 | 2010-02-11 | Siemens Communications Inc. | Eliminating unreachable subscribers in voice-over-ip networks |
WO2008051383A2 (en) * | 2006-10-19 | 2008-05-02 | Amgen Inc. | Use of alcohol co-solvents to improve pegylation reaction yields |
US7803769B2 (en) * | 2006-10-25 | 2010-09-28 | Amgen Inc. | OSK1 peptide analogs and pharmaceutical compositions |
US20080123083A1 (en) * | 2006-11-29 | 2008-05-29 | The Regents Of The University Of Michigan | System and Method for Photoacoustic Guided Diffuse Optical Imaging |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
WO2008070117A1 (en) * | 2006-12-04 | 2008-06-12 | Promedior, Inc. | Conjoint therapy for treating fibrotic diseases |
US20100166734A1 (en) * | 2006-12-20 | 2010-07-01 | Edward Dolk | Oral delivery of polypeptides |
KR100888022B1 (en) | 2006-12-21 | 2009-03-09 | 재단법인 목암생명공학연구소 | Fusion Proteion of Imunoglobulin Fc and Human Apolipoproteina Kringle Fragment |
US8754194B2 (en) * | 2006-12-22 | 2014-06-17 | Csl Behring Gmbh | Modified coagulation factors with prolonged in vivo half-life |
WO2008095004A2 (en) | 2007-01-31 | 2008-08-07 | Affymax, Inc. | Nitrogen-based linkers for attaching modifying groups to polypeptides and other macromolecules |
DK2109457T3 (en) * | 2007-02-12 | 2016-04-11 | Csl Behring Gmbh | THERAPEUTIC USE OF KAZAL TYPE SERINE PROTEASE INHIBITORS |
US8895004B2 (en) | 2007-02-27 | 2014-11-25 | AbbVie Deutschland GmbH & Co. KG | Method for the treatment of amyloidoses |
US8501678B2 (en) | 2007-03-06 | 2013-08-06 | Atara Biotherapeutics, Inc. | Variant activin receptor polypeptides and uses thereof |
TWI454479B (en) | 2007-03-06 | 2014-10-01 | Amgen Inc | Variant activin receptor polypeptides and uses thereof |
DK2152736T3 (en) | 2007-05-03 | 2017-09-18 | Lysomab Gmbh | Complement factor H-derived short-consensus repeat (SCR) antibody constructs |
NZ581395A (en) * | 2007-05-14 | 2012-08-31 | Biogen Idec Inc | Single-chain fc (scfc) regions, binding polypeptides comprising same, and methods related thereto |
WO2008153745A2 (en) | 2007-05-22 | 2008-12-18 | Amgen Inc. | Compositions and methods for producing bioactive fusion proteins |
PE20090329A1 (en) * | 2007-05-30 | 2009-03-27 | Abbott Lab | HUMANIZED ANTIBODIES AGAINST GLOBULOMER AB (20-42) AND ITS USES |
US20090232801A1 (en) * | 2007-05-30 | 2009-09-17 | Abbot Laboratories | Humanized Antibodies Which Bind To AB (1-42) Globulomer And Uses Thereof |
EP2165716B1 (en) * | 2007-06-05 | 2014-11-12 | Oriental Yeast Co., Ltd. | Novel bone mass increasing agent |
WO2008157824A2 (en) * | 2007-06-21 | 2008-12-24 | Conjuchem Biotechnologies Inc. | Thrombopoietin peptide conjugates |
US8497243B2 (en) * | 2007-07-06 | 2013-07-30 | Promedior, Inc. | Methods and compositions useful in the treatment of mucositis |
US9884899B2 (en) * | 2007-07-06 | 2018-02-06 | Promedior, Inc. | Methods for treating fibrosis using CRP antagonists |
WO2009014726A1 (en) | 2007-07-26 | 2009-01-29 | The Regents Of The University Of California | Methods for enhancing bacterial cell display of proteins and peptides |
EP2489730B1 (en) | 2007-07-26 | 2015-12-30 | Amgen, Inc | Modified lecithin-cholesterol acyltransferase enzymes |
BRPI0814465B1 (en) | 2007-07-26 | 2021-11-23 | Novagen Holding Corporation | FUSION PROTEIN, DIMER, METHOD FOR PRODUCING A FUSION PROTEIN, CELL LINEAGE, USES OF A FUSION PROTEIN AND A PHARMACEUTICAL COMPOSITION AND PHARMACEUTICAL COMPOSITION |
JP2010535788A (en) * | 2007-08-09 | 2010-11-25 | シントニックス・ファーマシューティカルズ・インコーポレーテッド | Immunomodulatory peptides |
CA2696049A1 (en) * | 2007-08-17 | 2009-02-26 | Amgen Inc. | Formulations of antibodies and fc-fusion molecules using polycations |
EP2615114B1 (en) | 2007-08-23 | 2022-04-06 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
JOP20080381B1 (en) | 2007-08-23 | 2023-03-28 | Amgen Inc | Antigen Binding Proteins to Proprotein Convertase subtillisin Kexin type 9 (pcsk9) |
WO2009033212A1 (en) * | 2007-09-11 | 2009-03-19 | Christopher Hovens | The use of estrogen and androgen binding proteins in methods and compositions for treating gynaecological cancers |
AU2008304111B2 (en) | 2007-09-27 | 2014-04-24 | Amgen Inc. | Pharmaceutical formulations |
KR20100094453A (en) * | 2007-10-02 | 2010-08-26 | 포텐시아 팔마큐티칼스, 인크. | Sustained delivery of compstatin analogs from gels |
US7829735B2 (en) | 2007-10-26 | 2010-11-09 | Northwestern University | Universal phosphoramidite for preparation of modified biomolecules and surfaces |
ES2962777T3 (en) | 2007-11-15 | 2024-03-21 | Amgen Inc | Antioxidant-stabilized aqueous antibody formulation for parenteral administration |
US8414893B2 (en) | 2007-12-21 | 2013-04-09 | Amgen Inc. | Anti-amyloid antibodies and uses thereof |
EP4098661A1 (en) | 2007-12-26 | 2022-12-07 | Xencor, Inc. | Fc variants with altered binding to fcrn |
US20140127200A1 (en) * | 2008-01-03 | 2014-05-08 | The Scripps Research Institute | Multispecific Antibody Targeting and Multivalency Through Modular Recognition Domains |
JP5701064B2 (en) | 2008-01-25 | 2015-04-15 | アムジエン・インコーポレーテツド | Ferroportin antibody and method of use thereof |
JO2913B1 (en) | 2008-02-20 | 2015-09-15 | امجين إنك, | Antibodies directed to angiopoietin-1 and angiopoietin-2 and uses thereof |
CN101518644B (en) * | 2008-02-26 | 2011-07-13 | 上海交通大学医学院附属第九人民医院 | Application of Ang-2 and genes thereof in pharmacy |
KR101582841B1 (en) * | 2008-02-27 | 2016-01-11 | 노보 노르디스크 에이/에스 | Conjugated factor viii molecules |
US8962803B2 (en) | 2008-02-29 | 2015-02-24 | AbbVie Deutschland GmbH & Co. KG | Antibodies against the RGM A protein and uses thereof |
WO2009126944A1 (en) * | 2008-04-11 | 2009-10-15 | Trubion Pharmaceuticals, Inc. | Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
SG190572A1 (en) | 2008-04-29 | 2013-06-28 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
US9315577B2 (en) | 2008-05-01 | 2016-04-19 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
US8293714B2 (en) * | 2008-05-05 | 2012-10-23 | Covx Technology Ireland, Ltd. | Anti-angiogenic compounds |
JP5890174B2 (en) | 2008-05-09 | 2016-03-22 | アッヴィ・ドイチュラント・ゲー・エム・ベー・ハー・ウント・コー・カー・ゲー | Antibody against terminal glycation end product receptor (RAGE) and use thereof |
US20110076723A1 (en) * | 2008-05-23 | 2011-03-31 | Samsung Electronics Co., Ltd. | Antibody-peptide fused synergibody |
RU2010153580A (en) | 2008-06-03 | 2012-07-20 | Эбботт Лэборетриз (Us) | IMMUNOGLOBULINS WITH TWO VARIABLE DOMAINS AND THEIR APPLICATION |
US9109026B2 (en) | 2008-06-03 | 2015-08-18 | Abbvie, Inc. | Dual variable domain immunoglobulins and uses thereof |
JOP20190083A1 (en) | 2008-06-04 | 2017-06-16 | Amgen Inc | Fgf21 mutant fusion polypeptides and uses thereof |
KR101507718B1 (en) * | 2008-06-24 | 2015-04-10 | 체에스엘 베링 게엠베하 | Factor VIII, von Willebrand factor or complexes thereof with prolonged in vivo half-life |
EP2307456B1 (en) | 2008-06-27 | 2014-10-15 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
MX2010014574A (en) | 2008-07-08 | 2011-04-27 | Abbott Lab | Prostaglandin e2 dual variable domain immunoglobulins and uses thereof. |
AU2009274738B2 (en) | 2008-07-23 | 2012-12-13 | Hanmi Science Co., Ltd. | A polypeptide complex comprising non-peptidyl polymer having three functional ends |
US20100048488A1 (en) * | 2008-08-01 | 2010-02-25 | Syntonix Pharmaceuticals, Inc. | Immunomodulatory peptides |
EP2168590A1 (en) * | 2008-09-24 | 2010-03-31 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Antimicrobial peptides |
PT2331136T (en) * | 2008-09-26 | 2018-03-27 | Oncomed Pharm Inc | Frizzled-binding agents and uses thereof |
UA107921C2 (en) | 2008-11-26 | 2015-03-10 | Amgen Inc | Variants of polypeptide of receptor ivr activin and their use |
US20120121537A1 (en) * | 2009-01-12 | 2012-05-17 | Chaomin Sun | Methods and Compositions for Inhibiting Hepatitis C Virus Replication |
BRPI1007371A2 (en) * | 2009-01-29 | 2018-03-27 | Abbott Lab | il-1 binding proteins |
US20110165063A1 (en) * | 2009-01-29 | 2011-07-07 | Abbott Laboratories | Il-1 binding proteins |
US9238878B2 (en) | 2009-02-17 | 2016-01-19 | Redwood Bioscience, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
TWI541021B (en) | 2009-03-05 | 2016-07-11 | 艾伯維有限公司 | Il-17 binding proteins |
US8283162B2 (en) * | 2009-03-10 | 2012-10-09 | Abbott Laboratories | Antibodies relating to PIVKAII and uses thereof |
CA2754961C (en) * | 2009-03-11 | 2018-04-10 | Promedior, Inc. | Treatment and diagnostic methods for hypersensitive disorders |
AU2010224172B2 (en) * | 2009-03-11 | 2016-01-21 | Promedior, Inc. | Treatment methods for autoimmune disorders |
JP2012521197A (en) | 2009-03-20 | 2012-09-13 | アムジエン・インコーポレーテツド | Carrier immunoglobulin and use thereof |
CN102361632A (en) | 2009-03-30 | 2012-02-22 | 弗·哈夫曼-拉罗切有限公司 | Method for avoiding glass fogging |
AU2010230563A1 (en) | 2009-04-02 | 2011-09-22 | Roche Glycart Ag | Multispecific antibodies comprising full length antibodies and single chain Fab fragments |
AR076541A1 (en) | 2009-05-05 | 2011-06-22 | Amgen Inc | MUTANTS OF FGF21 AND USES OF THE SAME |
CA2760674A1 (en) | 2009-05-05 | 2010-11-11 | Amgen Inc. | Fgf21 mutants and uses thereof |
UA110323C2 (en) * | 2009-06-04 | 2015-12-25 | Promedior Inc | Derivative of serum amyloid p and their receipt and application |
HUE025294T2 (en) * | 2009-06-15 | 2016-02-29 | Biokine Therapeutics Ltd | Novel chemokine binding polypeptides capable of inhibiting the course of autoimmunity, inflammation and cancer |
JP2012530493A (en) | 2009-06-17 | 2012-12-06 | アムジエン・インコーポレーテツド | Chimeric polypeptides and uses thereof |
ES2708823T3 (en) | 2009-06-17 | 2019-04-11 | Promedior Inc | SAP variants and their use |
WO2011005488A1 (en) * | 2009-06-22 | 2011-01-13 | Amgen Inc. | Refolding proteins using a chemically controlled redox state |
EP3660032A1 (en) | 2009-06-25 | 2020-06-03 | Amgen, Inc | Capture purification processes for proteins expressed in a non-mammalian system |
EP2448965A4 (en) | 2009-07-02 | 2015-02-11 | Angiochem Inc | Multimeric peptide conjugates and uses thereof |
IT1395137B1 (en) * | 2009-08-05 | 2012-09-05 | Spider Biotech S R L | NEW ANTIPATOGENIC PEPTIDES |
CN105131112A (en) | 2009-08-29 | 2015-12-09 | Abbvie公司 | Therapeutic dll4 binding proteins |
WO2011028811A2 (en) | 2009-09-01 | 2011-03-10 | Abbott Laboratories | Dual variable domain immunoglobulins and uses thereof |
WO2011028952A1 (en) | 2009-09-02 | 2011-03-10 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
NZ701769A (en) | 2009-09-16 | 2016-06-24 | Genentech Inc | Coiled coil and/or tether containing protein complexes and uses thereof |
WO2011038139A1 (en) | 2009-09-23 | 2011-03-31 | Amgen Inc. | Treatment of ovarian cancer using a specific binding agent of human angiopoietin-2 in combination with a taxane |
US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
EP2480888B1 (en) | 2009-09-25 | 2016-11-30 | XOMA Technology Ltd. | Screening methods |
CN102666875A (en) | 2009-10-15 | 2012-09-12 | 雅培制药有限公司 | Dual variable domain immunoglobulins and uses thereof |
UY32979A (en) | 2009-10-28 | 2011-02-28 | Abbott Lab | IMMUNOGLOBULINS WITH DUAL VARIABLE DOMAIN AND USES OF THE SAME |
US8420083B2 (en) * | 2009-10-31 | 2013-04-16 | Abbvie Inc. | Antibodies to receptor for advanced glycation end products (RAGE) and uses thereof |
WO2011053982A2 (en) | 2009-11-02 | 2011-05-05 | University Of Washington | Therapeutic nuclease compositions and methods |
CA2780761A1 (en) | 2009-11-13 | 2011-05-19 | Puget Sound Blood Center | Factor viii t cell epitope variants having reduced immunogenicity |
NZ600278A (en) * | 2009-11-13 | 2014-04-30 | Grifols Therapeutics Inc | Von willebrand factor (vwf)-containing preparations, and methods, kits, and uses related thereto |
CA2781532A1 (en) | 2009-11-20 | 2011-05-26 | Amgen Inc. | Anti-orai1 antigen binding protein that binds the second extracellular loop of orai1 |
US20150359850A1 (en) | 2009-11-25 | 2015-12-17 | Santa Maria Biotherapeutics, Inc. | Administration of an anti-activin-a compound to a subject |
UA109888C2 (en) | 2009-12-07 | 2015-10-26 | ANTIBODY OR ANTIBODILITY ANTIBODY OR ITS BINDING TO THE β-CLOTE, FGF RECEPTORS AND THEIR COMPLEXES | |
AU2010329955A1 (en) | 2009-12-08 | 2012-05-24 | Abbott Gmbh & Co. Kg | Monoclonal antibodies against the RGM A protein for use in the treatment of retinal nerve fiber layer degeneration |
CN105693861A (en) | 2009-12-29 | 2016-06-22 | 新兴产品开发西雅图有限公司 | Heterodimer binding protein and application thereof |
TWI535445B (en) | 2010-01-12 | 2016-06-01 | 安可美德藥物股份有限公司 | Wnt antagonists and methods of treatment and screening |
CN102947341B (en) | 2010-01-19 | 2018-07-06 | 哈佛大学校长及研究员协会 | For pathogen detection and the engineering opsonin for the treatment of |
US8362210B2 (en) | 2010-01-19 | 2013-01-29 | Xencor, Inc. | Antibody variants with enhanced complement activity |
KR101784539B1 (en) | 2010-01-28 | 2017-10-11 | 랩터 파마슈티컬스 인코포레이티드 | Method for treating liver disorders with receptor associated protein (rap) peptide-fucosidase inhibitor conjugates |
JP2013519699A (en) | 2010-02-16 | 2013-05-30 | ノヴォ ノルディスク アー/エス | Factor VIII fusion protein |
WO2011109415A2 (en) | 2010-03-02 | 2011-09-09 | Amgen Inc. | Reducing viscosity of pharmaceutical formulations |
KR20180044441A (en) | 2010-03-02 | 2018-05-02 | 애브비 인코포레이티드 | Therapeutic dll4 binding proteins |
EP2542571B1 (en) | 2010-03-03 | 2016-05-25 | The University of British Columbia | Oligomer-specific amyloid beta epitope and antibodies |
TW201138821A (en) | 2010-03-26 | 2011-11-16 | Roche Glycart Ag | Bispecific antibodies |
CA2794745A1 (en) | 2010-03-29 | 2011-10-06 | Zymeworks, Inc. | Antibodies with enhanced or suppressed effector function |
KR20130043102A (en) | 2010-04-01 | 2013-04-29 | 온코메드 파마슈티칼스, 인크. | Frizzled-binding agents and uses thereof |
EP2371857A1 (en) | 2010-04-01 | 2011-10-05 | CSL Behring GmbH | Factor XII inhibitors for treating interstitial lung disease |
AR081755A1 (en) * | 2010-04-02 | 2012-10-17 | Hanmi Holdings Co Ltd | FORMULATION OF PROLONGED ACTION OF THE FOLICULES STIMULATING HORMONE WHERE AN IMMUNOGLOBULIN FRAGMENT, PREPARATION METHOD AND METHOD TO TREAT A SUBJECT SUFFERING A REPRODUCTIVE DISORDER ARE USED |
EP2556086B1 (en) * | 2010-04-09 | 2015-03-04 | Amgen Inc. | Btnl9 proteins, nucleic acids, and antibodies and uses thereof |
EP2558497A2 (en) | 2010-04-15 | 2013-02-20 | Amgen Inc. | Human fgf receptor and beta-klotho binding proteins |
WO2011130377A2 (en) | 2010-04-15 | 2011-10-20 | Abbott Laboratories | Amyloid-beta binding proteins |
TWI586806B (en) | 2010-04-23 | 2017-06-11 | 建南德克公司 | Production of heteromultimeric proteins |
LT2571532T (en) | 2010-05-14 | 2017-08-10 | Abbvie Inc. | Il-1 binding proteins |
JP2013528599A (en) | 2010-05-14 | 2013-07-11 | アムジェン インコーポレイテッド | Enhanced death receptor agonist |
CN102260343A (en) | 2010-05-25 | 2011-11-30 | 健能隆医药技术(上海)有限公司 | Application of recombinant human G-CSF dimer for treating nerve damage disease |
US20110305670A1 (en) * | 2010-06-10 | 2011-12-15 | President And Fellows Of Harvard College | Nucleic acid encoding fusion polypeptides that prevent or inhibit hiv infection |
WO2012012141A1 (en) | 2010-06-30 | 2012-01-26 | Amgen Inc. | Scnn1a/tnfrsf1a fusion proteins in cancer |
US20120100166A1 (en) | 2010-07-15 | 2012-04-26 | Zyngenia, Inc. | Ang-2 Binding Complexes and Uses Thereof |
US9120862B2 (en) | 2010-07-26 | 2015-09-01 | Abbott Laboratories | Antibodies relating to PIVKA-II and uses thereof |
PE20131412A1 (en) | 2010-08-03 | 2014-01-19 | Abbvie Inc | IMMUNOGLOBULINS WITH DUAL VARIABLE DOMAIN AND USES OF THE SAME |
CN104474546A (en) | 2010-08-13 | 2015-04-01 | 弗·哈夫曼-拉罗切有限公司 | Antibodies to il-1beta and il-18, for treatment of disease |
CA2808187A1 (en) | 2010-08-14 | 2012-02-23 | Abbvie Inc. | Amyloid-beta binding proteins |
CN103068846B9 (en) | 2010-08-24 | 2016-09-28 | 弗·哈夫曼-拉罗切有限公司 | Bispecific antibodies comprising disulfide-stabilized Fv fragments |
TW201211252A (en) | 2010-08-26 | 2012-03-16 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
JP5976652B2 (en) | 2010-09-10 | 2016-08-24 | ワイス・エルエルシー | Non-lipidated variant of Neisseria meningitidis ORF2086 antigen |
US8993727B2 (en) | 2010-09-22 | 2015-03-31 | Amgen Inc. | Carrier immunoglobulins and uses thereof |
EA024507B1 (en) | 2010-09-28 | 2016-09-30 | Амилин Фармасьютикалс, Ллк | Highly soluble leptins |
US9023791B2 (en) | 2010-11-19 | 2015-05-05 | Novartis Ag | Fibroblast growth factor 21 mutations |
US20120275996A1 (en) | 2010-12-21 | 2012-11-01 | Abbott Laboratories | IL-1 Binding Proteins |
PE20141060A1 (en) | 2010-12-21 | 2014-09-26 | Abbvie Inc | IL-1 ALPHA AND BETA DUAL VARIABLE DOMAIN IMMUNOGLOBULINS AND THEIR USE |
EP2655413B1 (en) | 2010-12-23 | 2019-01-16 | F.Hoffmann-La Roche Ag | Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery |
CN103415621A (en) | 2011-01-14 | 2013-11-27 | 雷德伍德生物科技股份有限公司 | Aldehyde-tagged immunoglobulin polypeptides and method of use thereof |
SG10201600531TA (en) | 2011-01-24 | 2016-02-26 | Univ Singapore | Pathogenic mycobacteria-derived mannose-capped lipoarabinomannan antigen binding proteins |
US10689447B2 (en) | 2011-02-04 | 2020-06-23 | Genentech, Inc. | Fc variants and methods for their production |
BR112013019499B1 (en) | 2011-02-04 | 2023-01-10 | Genentech, Inc. | VARIANT HETERO-MULTIMERIC PROTEIN OR MODIFIED IGG ANTIBODY, METHOD FOR PRODUCING A VARIANT HETERO-MULTIMERIC PROTEIN OR MODIFIED IGG ANTIBODY, COMPOSITION, METHOD FOR PREPARING A HETERO-MULTIMERIC PROTEIN AND VARIANT HETERO-MULTIMERIC PROTEIN |
US20120213781A1 (en) | 2011-02-11 | 2012-08-23 | Zyngenia, Inc. | Monovalent and Multivalent Multispecific Complexes and Uses Thereof |
EP2681238A2 (en) | 2011-02-28 | 2014-01-08 | Istituto di Ricovero E Cura A Carattere Scientifico Materno-Infantile Burlo Garofolo- Ospedale di Alta Specializzazione E di Rilievo | Apoptosis-inducing molecules and uses therefor |
CN103415301A (en) | 2011-03-09 | 2013-11-27 | 德国杰特贝林生物制品有限公司 | Factor xii inhibitors for the administration with medical procedures comprising contact with artificial surfaces |
EP2497489A1 (en) | 2011-03-09 | 2012-09-12 | CSL Behring GmbH | Factor XII inhibitors for the treatment of silent brain ischemia and ischemia of other organs |
PE20140593A1 (en) | 2011-03-16 | 2014-05-10 | Amgen Inc | POWERFUL AND SELECTIVE INHIBITORS OF NAV1.3 AND NAV1.7 |
AU2012239997A1 (en) | 2011-04-07 | 2013-10-17 | Amgen Inc. | Novel EGFR binding proteins |
ES2654057T3 (en) * | 2011-04-25 | 2018-02-12 | Taiho Pharmaceutical Co., Ltd. | Nanoparticles containing a pH sensitive peptide |
SI2704737T1 (en) | 2011-04-29 | 2018-06-29 | University Of Washington | Therapeutic nuclease compositions and methods |
JOP20200043A1 (en) | 2011-05-10 | 2017-06-16 | Amgen Inc | Methods of treating or preventing cholesterol related disorders |
CA2837169C (en) | 2011-05-24 | 2021-11-09 | Zyngenia, Inc. | Multispecific complexes comprising angiopoietin-2-binding peptide and their uses |
UA126465C2 (en) | 2011-06-10 | 2022-10-12 | Ханмі Сайенс Ко., Лтд. | A peptide having oxyntomodulin activity and a pharmaceutical composition for the treatment of obesity containing it |
EP3502129B1 (en) | 2011-06-17 | 2021-04-07 | Hanmi Science Co., Ltd. | A conjugate comprising oxyntomodulin and an immunoglobulin fragment, and use thereof |
EP2726088B1 (en) | 2011-06-29 | 2019-01-02 | Amgen Inc. | Predictive biomarker of survival in the treatment of renal cell carcinoma |
US9738707B2 (en) | 2011-07-15 | 2017-08-22 | Biogen Ma Inc. | Heterodimeric Fc regions, binding molecules comprising same, and methods relating thereto |
EP2734546A1 (en) | 2011-07-18 | 2014-05-28 | Amgen Inc. | Apelin antigen-binding proteins and uses thereof |
US9593160B2 (en) | 2011-07-18 | 2017-03-14 | President And Fellows Of Harvard College | Engineered microbe-targeting molecules and uses thereof |
AU2012286048A1 (en) | 2011-07-18 | 2014-02-20 | Arts Biologics A/S | Long acting luteinizing hormone (LH) compound |
IL230564B2 (en) | 2011-07-22 | 2023-09-01 | Csl Ltd | Inhibitory anti-factor xii/xiia monoclonal antibodies, methods of producing the same, pharmaceutical compositions containing the same and medical uses |
US9642917B2 (en) | 2011-07-25 | 2017-05-09 | Generon (Shanghai) Corporation, Ltd. | Use of G-CSF dimer in preparation of medicament for treatment of neurodegenerative diseases |
EP2744828A4 (en) | 2011-08-16 | 2014-12-31 | Univ Emory | Jaml specific binding agents, antibodies, and uses related thereto |
CA2846030A1 (en) * | 2011-08-31 | 2013-03-07 | Indi Molecular, Inc. | Vegf-specific capture agents, compositions and methods of using and making |
DE102012016127A1 (en) | 2011-08-31 | 2013-02-28 | Daniel Elias | Error correction encoding apparatus for data stream, supplies one of m' mutually different synchronous words to each block in error correction information |
EP2750989A1 (en) | 2011-09-02 | 2014-07-09 | Amgen Inc. | Pharmaceutical product and method of analysing light exposure of a pharmaceutical product |
TWI593708B (en) | 2011-09-26 | 2017-08-01 | 諾華公司 | Fusion proteins for treating metabolic disorders |
PL3418306T3 (en) | 2011-10-11 | 2024-04-15 | F. Hoffmann-La Roche Ag | Improved assembly of bispecific antibodies |
KR20140084254A (en) | 2011-10-24 | 2014-07-04 | 애브비 인코포레이티드 | Bispecific immunobinders directed against tnf and il-17 |
AR088512A1 (en) | 2011-10-24 | 2014-06-18 | Abbvie Inc | ANTIBODIES DIRECTED AGAINST TNF |
KR102091294B1 (en) | 2011-10-26 | 2020-04-16 | 암젠 인크 | Methods of reducing or eliminating protein modification and degradation arising from exposure to uv light |
CN102516393B (en) * | 2011-11-30 | 2017-03-15 | 北京康明百奥新药研发有限公司 | Insulin-simulated peptide fusion protein and mutant and its application |
EP2791173B1 (en) | 2011-12-14 | 2020-07-29 | AbbVie Deutschland GmbH & Co. KG | Composition and method for the diagnosis and treatment of iron-related disorders |
KR20140108562A (en) | 2011-12-19 | 2014-09-11 | 암젠 인코퍼레이티드 | Variant activin receptor polypeptides, alone or in combination with chemotherapy, and uses thereof |
SI2794626T1 (en) | 2011-12-22 | 2018-02-28 | Glycomimetics, Inc. | E-selectin antagonist compounds |
CN102558358A (en) * | 2011-12-30 | 2012-07-11 | 张海涛 | Preparation and application of human fibroblast growth factor 21 fusion protein and mutant of human fibroblast growth factor 21 fusion protein |
TW201333035A (en) | 2011-12-30 | 2013-08-16 | Abbvie Inc | Dual specific binding proteins directed against IL-13 and/or IL-17 |
EP3338617B1 (en) | 2012-01-23 | 2020-08-19 | Washington University | Goggle imaging systems and devices |
KR102129234B1 (en) | 2012-01-27 | 2020-07-02 | 아비에 도이치란트 게엠베하 운트 콤파니 카게 | Composition and method for the diagnosis and treatment of disease associated with neurite degeneration |
EP2623110A1 (en) | 2012-01-31 | 2013-08-07 | CSL Behring GmbH | Factor XII inhibitors for the treatment of neurological inflammatory disorders |
MX2014009565A (en) | 2012-02-10 | 2014-11-10 | Genentech Inc | Single-chain antibodies and other heteromultimers. |
PL2814502T3 (en) | 2012-02-15 | 2018-02-28 | Csl Behring Gmbh | Von willebrand factor variants having improved factor viii binding affinity |
EP2816893A1 (en) | 2012-02-22 | 2014-12-31 | Amgen Inc. | Autologous mammalian models derived from induced pluripotent stem cells and related methods |
EP3485906A1 (en) | 2012-03-09 | 2019-05-22 | Pfizer Inc | Neisseria meningitidis compositions and methods thereof |
SA115360586B1 (en) | 2012-03-09 | 2017-04-12 | فايزر انك | Neisseria meningitidis compositions and methods thereof |
CA2867631C (en) | 2012-03-28 | 2019-06-11 | Amgen Inc. | Dr5 receptor agonist combinations |
US9809641B2 (en) * | 2012-04-23 | 2017-11-07 | Nrl Pharma, Inc. | Lactoferrin fusion protein and method for preparation thereof |
EA039663B1 (en) | 2012-05-03 | 2022-02-24 | Амген Инк. | Use of an anti-pcsk9 antibody for lowering serum cholesterol ldl and treating cholesterol related disorders |
EP2846822A2 (en) | 2012-05-11 | 2015-03-18 | Prorec Bio AB | Method for diagnosis and treatment of prolactin associated disorders |
CN104302177B (en) | 2012-05-17 | 2019-05-28 | 延伸生物科学股份有限公司 | Carrier for improved drug delivery |
KR20150030706A (en) | 2012-06-11 | 2015-03-20 | 암젠 인코퍼레이티드 | Dual receptor antagonistic antigen-binding proteins and uses thereof |
RU2015100656A (en) | 2012-06-27 | 2016-08-20 | Ф. Хоффманн-Ля Рош Аг | METHOD FOR PRODUCING ANTIBODY FC-FRAGMENT CONNECTING, INCLUDING AT LEAST ONE CONNECTING GROUP, WHICH SPECIALLY RELATED TO THE TARGET, AND THEIR APPLICATION |
KR20150023889A (en) | 2012-06-27 | 2015-03-05 | 에프. 호프만-라 로슈 아게 | Method for selection and production of tailor-made highly selective and multi-specific targeting entities containing at least two different binding entities and uses thereof |
WO2014011955A2 (en) | 2012-07-12 | 2014-01-16 | Abbvie, Inc. | Il-1 binding proteins |
CN104703999A (en) | 2012-07-19 | 2015-06-10 | 安姆根有限公司 | Human BTNl3 proteins, nucleic acids, and antibodies and uses thereof |
KR101968344B1 (en) | 2012-07-25 | 2019-04-12 | 한미약품 주식회사 | A composition for treating hyperlipidemia comprising oxyntomodulin analog |
BR112015008663B1 (en) * | 2012-10-17 | 2021-01-12 | CSL Behring Lengnau AG | USE OF AN EFFECTIVE AMOUNT OF A POLYMERIC PROTEIN UNDERSTANDING SIX POLYMEPTIDE DEMONOMER UNITS |
AU2013334790A1 (en) | 2012-10-23 | 2015-04-30 | Oncomed Pharmaceuticals, Inc. | Methods of treating neuroendocrine tumors using Wnt pathway-binding agents |
KR20190107184A (en) | 2012-11-01 | 2019-09-18 | 애브비 인코포레이티드 | Anti-vegf/dll4 dual variable domain immunoglobulins and uses thereof |
KR101993393B1 (en) | 2012-11-06 | 2019-10-01 | 한미약품 주식회사 | A composition for treating diabetes or diabesity comprising oxyntomodulin analog |
KR102311517B1 (en) | 2012-11-06 | 2021-10-14 | 한미약품 주식회사 | Liquid formulation of protein conjugate comprising the oxyntomodulin and an immunoglobulin fragment |
AU2013355238B2 (en) | 2012-12-07 | 2017-12-14 | Glycomimetics, Inc. | Compounds, compositions and methods using E-selectin antagonists for mobilization of hematopoietic cells |
EP2935311B1 (en) | 2012-12-20 | 2021-03-31 | Amgen Inc. | Apj receptor agonists and uses thereof |
US10632179B2 (en) * | 2013-01-11 | 2020-04-28 | Case Western Reserve University | Methods and compositions for treating cancer |
KR102073748B1 (en) | 2013-01-31 | 2020-02-05 | 한미약품 주식회사 | Recombinant yeast transformant and process for preparing immunoglobulin Fc fragment employing the same |
JP2016510411A (en) | 2013-02-04 | 2016-04-07 | オンコメッド ファーマシューティカルズ インコーポレイテッド | Methods and monitoring of treatment with WNT pathway inhibitors |
MX366400B (en) * | 2013-02-26 | 2019-07-08 | Hanmi Pharm Ind Co Ltd | Novel insulin analog and use thereof. |
RU2627175C2 (en) | 2013-03-08 | 2017-08-03 | Тайхо Фармасьютикал Ко., Лтд. | Novel peptide with 5 linked ctl epitopes |
ES2844189T3 (en) | 2013-03-08 | 2021-07-21 | Csl Behring Gmbh | Treatment and prevention of remote ischemia-reperfusion injuries |
US10344060B2 (en) | 2013-03-12 | 2019-07-09 | Amgen Inc. | Potent and selective inhibitors of Nav1.7 |
JOP20140087B1 (en) | 2013-03-13 | 2021-08-17 | Amgen Inc | Proteins specific for baff and b7rp1 and uses thereof |
SI2968461T1 (en) * | 2013-03-13 | 2023-01-31 | Genzyme Corporation | Fusion proteins comprising pdgf and vegf binding portions and methods of using thereof |
US9458246B2 (en) | 2013-03-13 | 2016-10-04 | Amgen Inc. | Proteins specific for BAFF and B7RP1 |
US9168300B2 (en) | 2013-03-14 | 2015-10-27 | Oncomed Pharmaceuticals, Inc. | MET-binding agents and uses thereof |
BR112015023797A2 (en) | 2013-03-15 | 2017-10-24 | Abbvie Inc | dual specificity binding proteins directed against il-1b and / or il-17 |
SG11201505926VA (en) | 2013-03-15 | 2015-09-29 | Biogen Ma Inc | Factor ix polypeptide formulations |
US10551379B2 (en) | 2013-03-15 | 2020-02-04 | President And Fellows Of Harvard College | Methods and compositions for improving detection and/or capture of a target entity |
EP2796145B1 (en) | 2013-04-22 | 2017-11-01 | CSL Ltd. | A covalent complex of von willebrand factor and faktor viii linked by a disulphide bridge |
JP6649250B2 (en) * | 2013-05-21 | 2020-02-19 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | Engineered heme binding constructs and uses thereof |
ES2753419T3 (en) | 2013-06-07 | 2020-04-08 | Univ Duke | Complement factor H inhibitors |
JP6267792B2 (en) | 2013-06-28 | 2018-01-24 | アムジエン・インコーポレーテツド | Methods for treating homozygous familial hypercholesterolemia |
PL3013366T3 (en) | 2013-06-28 | 2022-01-17 | Csl Behring Gmbh | Combination therapy using a factor xii inhibitor and a c1-inhibitor |
BR112016001376A2 (en) | 2013-07-25 | 2017-10-24 | Novartis Ag | synthetic apelin polypeptide bioconjugates |
SG11201600211XA (en) | 2013-07-25 | 2016-02-26 | Novartis Ag | Cyclic polypeptides for the treatment of heart failure |
KR20180099912A (en) | 2013-09-08 | 2018-09-05 | 화이자 인코포레이티드 | Neisseria meningitidis compositions and methods thereof |
CN105579467B (en) * | 2013-09-18 | 2021-03-09 | Bcn肽类股份有限公司 | Cortictatin analogues for the treatment of inflammatory and/or immune diseases |
US20160235810A1 (en) | 2013-10-18 | 2016-08-18 | Novartis Ag | Methods of treating diabetes and related disorders |
CA2927817C (en) | 2013-10-21 | 2019-02-26 | Taiho Pharmaceutical Co., Ltd. | Novel peptide having 4 linked ctl epitopes |
ES2759252T3 (en) | 2013-10-31 | 2020-05-08 | Resolve Therapeutics Llc | Nuclease-albumin fusions and therapeutic methods |
US10513546B2 (en) | 2013-12-18 | 2019-12-24 | President And Fellows Of Harvard College | CRP capture/detection of gram positive bacteria |
ES2902835T3 (en) | 2014-01-09 | 2022-03-30 | Hadasit Med Res Service | Improved cell compositions and methods for cancer therapy |
US20150291689A1 (en) | 2014-03-09 | 2015-10-15 | Abbvie, Inc. | Compositions and Methods for Treating Rheumatoid Arthritis |
PL3129406T3 (en) * | 2014-04-11 | 2019-07-31 | Medimmune, Llc | Conjugated compounds comprising cysteine-engineered antibodies |
CN106471117A (en) | 2014-05-06 | 2017-03-01 | 豪夫迈·罗氏有限公司 | Produce heteromultimeric albumen using mammalian cell |
CA2951391C (en) | 2014-06-10 | 2021-11-02 | Amgen Inc. | Apelin polypeptides |
WO2015191760A2 (en) | 2014-06-10 | 2015-12-17 | Abbvie, Inc. | Compositions and methods for treating rheumatoid arthritis |
CN106456778A (en) | 2014-06-18 | 2017-02-22 | 德国杰特贝林生物制品有限公司 | Therapy using a factor XII inhibitor in a neurotraumatic disorder |
CA2953593C (en) | 2014-07-02 | 2023-09-26 | Csl Limited | Modified von willebrand factor |
US10526391B2 (en) | 2014-07-22 | 2020-01-07 | The University Of Notre Dame Du Lac | Molecular constructs and uses thereof |
MX2017003247A (en) | 2014-09-15 | 2017-11-30 | Amgen Inc | Bi-specific anti-cgrp receptor/pac1 receptor antigen binding proteins and uses thereof. |
TWI772252B (en) | 2014-09-16 | 2022-08-01 | 南韓商韓美藥品股份有限公司 | Use of a long acting glp-1/glucagon receptor dual agonist for the treatment of non-alcoholic fatty liver disease |
EP3207146B1 (en) | 2014-10-15 | 2021-09-29 | Amgen Inc. | Promoter and regulatory elements for improved expression of heterologous genes in host cells |
JP6946182B2 (en) | 2014-10-22 | 2021-10-06 | エクステンド バイオサイエンシズ インコーポレーテッドExtend Biosciences, Inc | Therapeutic Vitamin D Conjugate |
WO2016065052A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Insulin vitamin d conjugates |
US9789197B2 (en) | 2014-10-22 | 2017-10-17 | Extend Biosciences, Inc. | RNAi vitamin D conjugates |
WO2016065181A1 (en) | 2014-10-23 | 2016-04-28 | Amgen Inc. | Reducing viscosity of pharmaceutical formulations |
WO2016069889A1 (en) | 2014-10-31 | 2016-05-06 | Resolve Therapeutics, Llc | Therapeutic nuclease-transferrin fusions and methods |
WO2016087416A1 (en) | 2014-12-03 | 2016-06-09 | F. Hoffmann-La Roche Ag | Multispecific antibodies |
US10093733B2 (en) | 2014-12-11 | 2018-10-09 | Abbvie Inc. | LRP-8 binding dual variable domain immunoglobulin proteins |
CA2971672A1 (en) * | 2014-12-22 | 2016-06-30 | Morphosys Ag | Means and methods for displaying cyclic peptides on bacteriophage particles |
KR102418477B1 (en) | 2014-12-30 | 2022-07-08 | 한미약품 주식회사 | Gluagon Derivatives |
TW201639596A (en) | 2015-01-24 | 2016-11-16 | 艾伯維有限公司 | Compositions and methods for treating psoriatic arthritis |
CN107530454B (en) * | 2015-01-30 | 2021-10-26 | 犹他大学研究基金会 | Dimeric collagen hybrid peptides and methods of use |
US10888611B2 (en) | 2015-02-19 | 2021-01-12 | Pfizer Inc. | Neisseria meningitidis compositions and methods thereof |
US10711067B2 (en) | 2015-03-03 | 2020-07-14 | Xoma (Us) Llc | Treatment of post-prandial hyperinsulinemia and hypoglycemia after bariatric surgery |
IL254293B (en) * | 2015-03-05 | 2022-09-01 | Peter Und Traudl Engelhorn Stiftung Zur Forderung Der Lebenswissenschaften | System for presenting peptides on the cell surface |
EP3281010B1 (en) | 2015-04-10 | 2020-12-30 | The Regents of The University of California | Methods of determining patient populations amenable to immunomodulatory treatment of cancer |
US10857229B2 (en) | 2015-04-30 | 2020-12-08 | Amgen Inc. | Treatment of ovarian cancer in patients with ascites using a specific binding agent of human angiopoietin-2 in combination with a taxane |
WO2016179350A1 (en) | 2015-05-06 | 2016-11-10 | Washington University | Compounds having rd targeting motifs and methods of use thereof |
EP3298036B1 (en) | 2015-05-22 | 2022-04-06 | CSL Behring Lengnau AG | Methods for preparing modified von willebrand factor |
EP3297656B1 (en) | 2015-05-22 | 2020-01-08 | CSL Behring Lengnau AG | Truncated von willebrand factor polypeptides for treating hemophilia |
TW201710286A (en) | 2015-06-15 | 2017-03-16 | 艾伯維有限公司 | Binding proteins against VEGF, PDGF, and/or their receptors |
EP3307326B9 (en) | 2015-06-15 | 2021-02-24 | Angiochem Inc. | Methods for the treatment of leptomeningeal carcinomatosis |
WO2016209972A1 (en) | 2015-06-26 | 2016-12-29 | Amgen Inc. | Biomarker of survival in the treatment of renal cell carcinoma with a vegfr inhibitor and an ang2 inhibitor |
US10435457B2 (en) | 2015-08-06 | 2019-10-08 | President And Fellows Of Harvard College | Microbe-binding molecules and uses thereof |
AU2016323440B2 (en) | 2015-09-15 | 2023-07-13 | Amgen Inc. | Tetravalent bispecific and tetraspecific antigen binding proteins and uses thereof |
JP7002446B2 (en) | 2015-09-21 | 2022-03-04 | アプティーボ リサーチ アンド デベロップメント エルエルシー | CD3 binding polypeptide |
WO2017059371A1 (en) | 2015-10-01 | 2017-04-06 | Amgen Inc. | Treatment of bile acid disorders |
KR102146319B1 (en) | 2015-10-02 | 2020-08-25 | 에프. 호프만-라 로슈 아게 | Bispecific antibodies specific for PD1 and TIM3 |
WO2017075189A1 (en) | 2015-10-27 | 2017-05-04 | University Of Massachusetts | Factor h-fc immunotherapy |
KR101826792B1 (en) * | 2015-10-29 | 2018-02-09 | 주식회사 와이바이오로직스 | Composition for preventing or treating fatty liver or insulin resistance syndrome including extracellular domain of delta-like 1 homolog |
EP3390447A1 (en) | 2015-12-15 | 2018-10-24 | Amgen Inc. | Pacap antibodies and uses thereof |
CA3006748A1 (en) * | 2015-12-15 | 2017-06-22 | Sarepta Therapeutics, Inc. | Peptide oligonucleotide conjugates |
US10646465B2 (en) | 2015-12-17 | 2020-05-12 | Biokine Therapeutics Ltd. | Small molecules against cancer |
US11129824B2 (en) | 2015-12-17 | 2021-09-28 | Biokine Therapeutics Ltd. | Small molecules for inhibiting chemokine activity and/or cancer cells growth |
EP3184149A1 (en) | 2015-12-23 | 2017-06-28 | Julius-Maximilians-Universität Würzburg | Soluble glycoprotein v for treating thrombotic diseases |
SG11201805497QA (en) | 2016-01-07 | 2018-07-30 | Csl Behring Recombinant Facility Ag | Mutated truncated von willebrand factor |
WO2017117630A1 (en) | 2016-01-07 | 2017-07-13 | Csl Limited | Mutated von willebrand factor |
US11174321B2 (en) | 2016-04-06 | 2021-11-16 | Csl Limited | Method of treating atherosclerosis |
KR101975743B1 (en) * | 2016-04-07 | 2019-05-09 | 한양대학교 에리카산학협력단 | Vascular Endothelial Growth Factor Receptor Targeting Peptide-elastin Fusion Polypeptides and Their Self-assembled Nanostructures |
KR20180133463A (en) * | 2016-04-14 | 2018-12-14 | 타오 헬스 라이프 파마 가부시키가이샤 | Amylose ferroide (ASPD) binding inhibitory peptides, and evaluation and screening methods |
CN109071634A (en) | 2016-04-26 | 2018-12-21 | R.P.谢勒技术有限责任公司 | Antibody coupling matter and its preparation and application |
LT3458479T (en) | 2016-06-08 | 2021-02-25 | Abbvie Inc. | Anti-b7-h3 antibodies and antibody drug conjugates |
MA45554A (en) | 2016-07-01 | 2019-05-08 | Resolve Therapeutics Llc | OPTIMIZED BINUCLEASE FUSIONS. |
CN115925780A (en) | 2016-07-22 | 2023-04-07 | 美国安进公司 | Method for purifying Fc-containing protein |
CN106279437B (en) | 2016-08-19 | 2017-10-31 | 安源医药科技(上海)有限公司 | Hyperglycosylated human coagulation factor VIII fusion proteins and preparation method thereof and purposes |
CN107759697B (en) | 2016-08-19 | 2023-03-24 | 安源医药科技(上海)有限公司 | Method for producing fusion protein |
US11123438B2 (en) | 2016-08-19 | 2021-09-21 | Ampsource Biopharma Shanghai Inc. | Linker peptide for constructing fusion protein |
WO2018067987A1 (en) | 2016-10-06 | 2018-04-12 | Amgen Inc. | Reduced viscosity protein pharmaceutical formulations |
WO2018079702A1 (en) | 2016-10-28 | 2018-05-03 | 株式会社Nrlファーマ | Lactoferrin/albumin fusion protein and production method therefor |
SG11201903950UA (en) | 2016-11-11 | 2019-05-30 | CSL Behring Lengnau AG | Truncated von willebrand factor polypeptides for treating hemophilia |
WO2018087271A1 (en) | 2016-11-11 | 2018-05-17 | Csl Behring Recombinant Facility Ag | Truncated von willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder |
JP7274417B2 (en) | 2016-11-23 | 2023-05-16 | イミュノア・セラピューティクス・インコーポレイテッド | 4-1BB binding protein and uses thereof |
EP3496742A4 (en) * | 2016-12-01 | 2020-04-08 | University Of South Florida | Peptibodies, compositions thereof, and methods of treating atrial fibrillation |
CA3088131A1 (en) | 2017-01-13 | 2018-07-19 | Pietro P. Sanna | Methods and compositions for treating hpa hyperactivity |
SG10202111092UA (en) | 2017-01-31 | 2021-11-29 | Pfizer | Neisseria meningitidis compositions and methods thereof |
CN110536899B (en) | 2017-03-23 | 2023-12-12 | 韩美药品株式会社 | Insulin analogue complex with reduced affinity for insulin receptor and uses thereof |
CA3053357A1 (en) * | 2017-04-03 | 2018-10-11 | F. Hoffmann-La Roche Ag | Immunoconjugates of an anti-pd-1 antibody with a mutant il-2 or with il-15 |
KR102408873B1 (en) | 2017-04-05 | 2022-06-15 | 에프. 호프만-라 로슈 아게 | Bispecific antibodies specifically binding to pd1 and lag3 |
US10865238B1 (en) | 2017-05-05 | 2020-12-15 | Duke University | Complement factor H antibodies |
WO2018234518A1 (en) | 2017-06-22 | 2018-12-27 | CSL Behring Lengnau AG | Modulation of fviii immunogenicity by truncated vwf |
SG11202000503QA (en) | 2017-07-20 | 2020-02-27 | Aptevo Res & Development Llc | Antigen binding proteins binding to 5t4 and 4-1bb and related compositions and methods |
EP3658191A1 (en) | 2017-07-26 | 2020-06-03 | Janssen Pharmaceutica NV | Methods of protecting vascular integrity induced by targeted radiation therapy |
WO2019028012A2 (en) | 2017-07-31 | 2019-02-07 | Dana-Farber Cancer Institute, Inc. | Methods of using pembrolizumab and trebananib |
MX2020001327A (en) | 2017-08-04 | 2020-03-20 | Amgen Inc | Method of conjugation of cys-mabs. |
CN111164104A (en) | 2017-08-09 | 2020-05-15 | 麻省理工学院 | Albumin binding peptide conjugates and methods thereof |
WO2019036605A2 (en) | 2017-08-17 | 2019-02-21 | Massachusetts Institute Of Technology | Multiple specificity binders of cxc chemokines and uses thereof |
KR102578087B1 (en) | 2017-08-17 | 2023-09-18 | 저스트-에보텍 바이오로직스, 아이엔씨. | Method for purifying glycosylated proteins from host cell galectins and other contaminants |
MX2020002070A (en) | 2017-08-22 | 2020-03-24 | Sanabio Llc | Soluble interferon receptors and uses thereof. |
EP3727447A1 (en) | 2017-12-19 | 2020-10-28 | Massachusetts Institute of Technology | Antigen-adjuvant coupling reagents and methods of use |
US20210046189A1 (en) * | 2018-03-30 | 2021-02-18 | HANMl PHARM. CO., LTD. | Long-acting protein conjugates for brain targeting, a preparation method thereof, and a composition comprising the same |
US20220128474A1 (en) | 2018-10-23 | 2022-04-28 | Amgen Inc. | Automatic calibration and automatic maintenance of raman spectroscopic models for real-time predictions |
US20210395751A1 (en) | 2018-10-31 | 2021-12-23 | The University Of Sydney | Compositions and methods for treating viral infections |
CN113597319A (en) | 2019-01-04 | 2021-11-02 | 分解治疗有限责任公司 | Treatment of xerosis with nuclease fusion proteins |
CA3125552A1 (en) * | 2019-01-07 | 2020-07-16 | Cenna Biosciences Inc. | Novel peptides and uses thereof |
AU2020211412A1 (en) | 2019-01-25 | 2021-08-12 | Janssen Pharmaceutica Nv | Methods for mitigating liver injury and promoting liver hypertrophy, regeneration and cell engraftment in conjunction with radiation and/or radiomimetic treatments |
MA54821A (en) | 2019-01-25 | 2021-12-01 | Janssen Pharmaceutica Nv | METHODS FOR INCREASING PROTECTION AGAINST ORGAN AND VESSEL DAMAGE, HEMATOPOIETIC RECOVERY AND SURVIVAL IN RESPONSE TO EXPOSURE TO WHOLE BODY IRRADIATION OR CHEMICAL AGENTS |
KR20210120037A (en) | 2019-01-25 | 2021-10-06 | 잔센파마슈티카엔.브이. | Methods for mitigating the toxic effects of blistering agents and caustic gases |
CN116063520A (en) | 2019-01-30 | 2023-05-05 | 真和制药有限公司 | anti-GAL 3 antibodies and uses thereof |
WO2020168315A1 (en) | 2019-02-15 | 2020-08-20 | Just-Evotec Biologics, Inc. | Automated biomanufacturing systems, facilities, and processes |
US20230051872A1 (en) | 2019-03-22 | 2023-02-16 | Reflexion Pharmaceuticals, Inc. | Multivalent D-Peptidic Compounds for Target Proteins |
US20210061861A1 (en) | 2019-03-22 | 2021-03-04 | Reflexion Pharmaceuticals, Inc. | D-peptidic compounds for vegf |
KR20220009442A (en) | 2019-05-15 | 2022-01-24 | 아론바이오 리미티드 | Small molecules for cancer treatment, inhibition of chemokine activity and/or induction of cell death |
KR20220009984A (en) | 2019-05-17 | 2022-01-25 | 유니베르시태트 취리히 | Haptoglobin for use in the treatment of secondary neurological adverse events after hemorrhagic stroke |
MX2021014534A (en) | 2019-05-30 | 2022-02-11 | Amgen Inc | Engineering the hinge region to drive antibody dimerization. |
JP2022538974A (en) | 2019-06-26 | 2022-09-07 | マサチューセッツ インスチテュート オブ テクノロジー | Immunomodulatory fusion protein-metal hydroxide complexes and methods thereof |
AU2020304671A1 (en) | 2019-06-28 | 2022-01-20 | Amgen Inc. | Anti-CGRP receptor/anti-PAC1 receptor bispecific antigen binding proteins |
WO2021001522A1 (en) | 2019-07-04 | 2021-01-07 | CSL Behring Lengnau AG | A truncated von willebrand factor (vwf) for increasing the in vitro stability of coagulation factor viii |
MX2022001882A (en) | 2019-08-12 | 2022-05-30 | Aptevo Res & Development Llc | 4-1bb and ox40 binding proteins and related compositions and methods, antibodies against 4-1bb, antibodies against ox40. |
MX2022005566A (en) | 2019-11-08 | 2022-07-19 | Amgen Inc | Engineering charge pair mutations for pairing of hetero-igg molecules. |
US20220348637A1 (en) | 2019-11-11 | 2022-11-03 | CSL Behring Lengnau AG | Polypeptides for inducing tolerance to factor viii |
EP4072598A4 (en) | 2019-12-13 | 2024-02-21 | Washington University St Louis | Near infrared fluorescent dyes, formulations and related methods |
CA3164385A1 (en) | 2020-01-13 | 2021-07-22 | Aptevo Research And Development Llc | Formulations for protein therapeutics |
WO2021145946A1 (en) * | 2020-01-13 | 2021-07-22 | Invenra Inc. | Multispecific treg binding molecules |
WO2021158469A1 (en) | 2020-02-03 | 2021-08-12 | Amgen Inc. | Multivariate bracketing approach for sterile filter validation |
CA3165342A1 (en) | 2020-06-29 | 2022-01-06 | James Arthur Posada | Treatment of sjogren's syndrome with nuclease fusion proteins |
MX2023002125A (en) | 2020-08-20 | 2023-04-26 | Amgen Inc | Antigen binding proteins with non-canonical disulfide in fab region. |
US20230374162A1 (en) | 2020-10-07 | 2023-11-23 | Amgen Inc. | Rational selection of building blocks for the assembly of multispecific antibodies |
EP4244246A1 (en) | 2020-11-10 | 2023-09-20 | Amgen Inc. | Novel linkers of multispecific antigen binding domains |
KR20230110563A (en) | 2020-11-20 | 2023-07-24 | 체에스엘 베링 게엠베하 | Methods of treating antibody-mediated rejection |
EP4255574A1 (en) | 2020-12-01 | 2023-10-11 | Aptevo Research and Development LLC | Heterodimeric psma and cd3-binding bispecific antibodies |
MX2023007131A (en) | 2020-12-18 | 2023-06-27 | Richter Gedeon Nyrt | Methods for the purification of refolded fc-peptide fusion protein. |
AR124681A1 (en) | 2021-01-20 | 2023-04-26 | Abbvie Inc | ANTI-EGFR ANTIBODY-DRUG CONJUGATES |
WO2022162218A1 (en) | 2021-02-01 | 2022-08-04 | Csl Behring Ag | Method of treating or preventing an adverse secondary neurological outcome following a haemorrhagic stroke |
AU2022263406A1 (en) | 2021-04-20 | 2023-10-19 | Amgen Inc. | Balanced charge distribution in electrostatic steering of chain pairing in multi-specific and monovalent igg molecule assembly |
AU2022269297A1 (en) | 2021-05-07 | 2023-12-07 | Csl Behring Ag | Expression system for producing a recombinant haptoglobin (hp) beta chain |
KR20240024819A (en) | 2021-05-21 | 2024-02-26 | 압테보 리서치 앤드 디벨롭먼트 엘엘씨 | Dosage regimen of protein therapeutics |
WO2022266467A2 (en) | 2021-06-17 | 2022-12-22 | Dana-Farber Cancer Institute, Inc. | Recombinant histone polypeptide and uses thereof |
CA3234340A1 (en) | 2021-10-01 | 2023-04-06 | Janssen Pharmaceutica N.V. | Methods of increasing progenitor cell production |
US20230192843A1 (en) | 2021-10-14 | 2023-06-22 | Teneobio, Inc. | Mesothelin binding proteins and uses thereof |
AR127458A1 (en) | 2021-10-27 | 2024-01-24 | Amgen Inc | PREDICTION BASED ON DEEP LEARNING USING SPECTROSCOPY |
WO2023173084A1 (en) | 2022-03-11 | 2023-09-14 | University Of Rochester | Cyclopeptibodies and uses thereof |
WO2023180525A1 (en) | 2022-03-24 | 2023-09-28 | Richter Gedeon Nyrt. | Method for the manufacture of biopharmaceuticals |
WO2024026358A1 (en) | 2022-07-27 | 2024-02-01 | Teneobio, Inc. | Mesothelin binding proteins and uses thereof |
WO2024047219A1 (en) | 2022-09-02 | 2024-03-07 | Csl Behring Ag | Haptoglobin for use in treating or preventing exaggerated erectile response or erectile dysfunction |
Citations (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5098833A (en) * | 1989-02-23 | 1992-03-24 | Genentech, Inc. | DNA sequence encoding a functional domain of a lymphocyte homing receptor |
US5116964A (en) * | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
US5216131A (en) * | 1989-02-23 | 1993-06-01 | Genentech, Inc. | Lymphocyte homing receptors |
US5223409A (en) * | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
US5225538A (en) * | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
US5336603A (en) * | 1987-10-02 | 1994-08-09 | Genentech, Inc. | CD4 adheson variants |
US5338665A (en) * | 1991-10-16 | 1994-08-16 | Affymax Technologies N.V. | Peptide library and screening method |
US5432018A (en) * | 1990-06-20 | 1995-07-11 | Affymax Technologies N.V. | Peptide library and screening systems |
US5480981A (en) * | 1992-05-26 | 1996-01-02 | Immunex Corporation | CD30 ligand |
US5556335A (en) * | 1993-03-23 | 1996-09-17 | Holyoake Industries Limited | Thermally controlled diffusers |
US5608035A (en) * | 1994-02-02 | 1997-03-04 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
US5726290A (en) * | 1988-12-22 | 1998-03-10 | Genentech, Inc. | Soluble analogues of integrins |
US5733731A (en) * | 1991-10-16 | 1998-03-31 | Affymax Technologies N.V. | Peptide library and screening method |
US5739277A (en) * | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
US5773569A (en) * | 1993-11-19 | 1998-06-30 | Affymax Technologies N.V. | Compounds and peptides that bind to the erythropoietin receptor |
US5786331A (en) * | 1994-02-02 | 1998-07-28 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
US5869451A (en) * | 1995-06-07 | 1999-02-09 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
US5869452A (en) * | 1994-11-10 | 1999-02-09 | Monash University | Treatment of obesity |
US5877151A (en) * | 1989-07-05 | 1999-03-02 | The Board Of Regents Of The University Of Oklahoma | Method for inhibiting production of tumor necrosis factor |
US5880096A (en) * | 1994-02-02 | 1999-03-09 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
US5922545A (en) * | 1993-10-29 | 1999-07-13 | Affymax Technologies N.V. | In vitro peptide and antibody display libraries |
US5932546A (en) * | 1996-10-04 | 1999-08-03 | Glaxo Wellcome Inc. | Peptides and compounds that bind to the thrombopoietin receptor |
US5985599A (en) * | 1986-05-29 | 1999-11-16 | The Austin Research Institute | FC receptor for immunoglobulin |
US6919426B2 (en) * | 2002-09-19 | 2005-07-19 | Amgen Inc. | Peptides and related molecules that modulate nerve growth factor activity |
Family Cites Families (156)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3691016A (en) * | 1970-04-17 | 1972-09-12 | Monsanto Co | Process for the preparation of insoluble enzymes |
CA1023287A (en) * | 1972-12-08 | 1977-12-27 | Boehringer Mannheim G.M.B.H. | Process for the preparation of carrier-bound proteins |
US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US3941763A (en) * | 1975-03-28 | 1976-03-02 | American Home Products Corporation | PGlu-D-Met-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2 and intermediates |
US4195128A (en) * | 1976-05-03 | 1980-03-25 | Bayer Aktiengesellschaft | Polymeric carrier bound ligands |
US4330440A (en) * | 1977-02-08 | 1982-05-18 | Development Finance Corporation Of New Zealand | Activated matrix and method of activation |
CA1093991A (en) * | 1977-02-17 | 1981-01-20 | Hideo Hirohara | Enzyme immobilization with pullulan gel |
US4229537A (en) * | 1978-02-09 | 1980-10-21 | New York University | Preparation of trichloro-s-triazine activated supports for coupling ligands |
IN150740B (en) * | 1978-11-24 | 1982-12-04 | Hoffmann La Roche | |
US4289872A (en) * | 1979-04-06 | 1981-09-15 | Allied Corporation | Macromolecular highly branched homogeneous compound based on lysine units |
US4760067A (en) * | 1979-08-15 | 1988-07-26 | Merck & Co., Inc. | Allylsulfoxide enzyme inhibitors |
DE3175151D1 (en) | 1980-05-21 | 1986-09-25 | Teijin Ltd | Reactive polymer and process for the preparation thereof |
US4560649A (en) * | 1981-10-15 | 1985-12-24 | Cornell Research Foundation | Assaying for hLH or hCG with immobilized hormone receptors |
JPH0751511B2 (en) * | 1982-03-15 | 1995-06-05 | 味の素株式会社 | Cancer therapeutic agent containing interleukin-2 |
ATE37983T1 (en) | 1982-04-22 | 1988-11-15 | Ici Plc | DELAYED RELEASE AGENT. |
US4587046A (en) | 1982-05-18 | 1986-05-06 | The Regents Of The University Of California | Drug-carrier conjugates |
DE3380726D1 (en) * | 1982-06-24 | 1989-11-23 | Japan Chem Res | Long-acting composition |
US4966888A (en) * | 1985-07-08 | 1990-10-30 | Cornell Research Foundation, Inc. | hCG-hLH receptor and hCG-hLH receptor-hCG complex as antigens, antibodies thereto and contraceptive vaccine |
KR850004274A (en) * | 1983-12-13 | 1985-07-11 | 원본미기재 | Method for preparing erythropoietin |
NZ210501A (en) * | 1983-12-13 | 1991-08-27 | Kirin Amgen Inc | Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence |
US4522750A (en) * | 1984-02-21 | 1985-06-11 | Eli Lilly And Company | Cytotoxic compositions of transferrin coupled to vinca alkaloids |
DE3572982D1 (en) | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
SE470099B (en) * | 1984-05-17 | 1993-11-08 | Jerker Porath | Sulfone activated thioether adsorbents for separation of eg protein |
US4578335A (en) * | 1984-05-21 | 1986-03-25 | Immunex Corporation | Interleukin 2 receptor |
CA1283661C (en) * | 1984-06-20 | 1991-04-30 | Franz Jansen | Imidazolides, process for their preparation and application as intermediates for the synthesis of cytotoxic conjugates |
EP0173494A3 (en) | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Chimeric receptors by dna splicing and expression |
US4675285A (en) * | 1984-09-19 | 1987-06-23 | Genetics Institute, Inc. | Method for identification and isolation of DNA encoding a desired protein |
SE454885B (en) * | 1984-10-19 | 1988-06-06 | Exploaterings Ab Tbf | POLYMER COATED PARTICLES WITH IMMOBILIZED METAL ZONES IN ITS SURFACE PROCEDURES FOR PRODUCING THEREOF |
US4959314A (en) * | 1984-11-09 | 1990-09-25 | Cetus Corporation | Cysteine-depleted muteins of biologically active proteins |
EP0206448B1 (en) * | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
US4917888A (en) * | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
CA1283046C (en) | 1986-05-29 | 1991-04-16 | Nandini Katre | Tumor necrosis factor formulation |
US4791192A (en) * | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
EP0318512B1 (en) * | 1986-08-18 | 1998-06-17 | Emisphere Technologies, Inc. | Delivery systems for pharmacological agents |
US4931544A (en) * | 1986-09-04 | 1990-06-05 | Cetus Corporation | Succinylated interleukin-2 for pharmaceutical compositions |
IL80005A (en) * | 1986-09-10 | 1992-11-15 | Yeda Res & Dev | Compositions for modulating the effect of tnf and il-1 |
US5229490A (en) * | 1987-05-06 | 1993-07-20 | The Rockefeller University | Multiple antigen peptide system |
US5359032A (en) * | 1987-08-26 | 1994-10-25 | Biogen Inc. | Interkeukin-1 inhibitor |
IL83878A (en) * | 1987-09-13 | 1995-07-31 | Yeda Res & Dev | Soluble protein corresponding to tnf inhibitory protein its preparation and pharmaceutical compositions containing it |
US5512544A (en) * | 1987-09-13 | 1996-04-30 | Yeda Research And Development Co. Ltd. | Pharmaceutical compositions comprising an anticytokine |
US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
US4847325A (en) * | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
US5153265A (en) * | 1988-01-20 | 1992-10-06 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
EP0325224B1 (en) | 1988-01-22 | 1996-07-31 | ZymoGenetics, Inc. | Methods of producing secreted receptor analogs |
US6018026A (en) * | 1988-01-22 | 2000-01-25 | Zymogenetics, Inc. | Biologically active dimerized and multimerized polypeptide fusions |
GB8807803D0 (en) | 1988-03-31 | 1988-05-05 | Glaxo Group Ltd | Biochemical product |
US5214131A (en) * | 1988-05-06 | 1993-05-25 | Sumitomo Pharmaceuticals Company, Limited | Polyethylene glycol derivatives, modified peptides and production thereof |
US5075222A (en) * | 1988-05-27 | 1991-12-24 | Synergen, Inc. | Interleukin-1 inhibitors |
US5359037A (en) * | 1988-09-12 | 1994-10-25 | Yeda Research And Development Co. Ltd. | Antibodies to TNF binding protein I |
US5811261A (en) * | 1988-09-12 | 1998-09-22 | Yeda Research And Development Co. Ltd. | Expression of the recombinant tumor necrosis factor binding protein I (TBP-I) |
US5681566A (en) * | 1988-10-24 | 1997-10-28 | 3I Research Exploitation Limited | Antibody conjugates with two or more covalently linked FC regions |
US5162430A (en) * | 1988-11-21 | 1992-11-10 | Collagen Corporation | Collagen-polymer conjugates |
JPH04502011A (en) | 1988-11-23 | 1992-04-09 | ジェネンテク,インコーポレイテッド | polypeptide derivative |
AU645745B2 (en) * | 1988-12-22 | 1994-01-27 | Xoma Corporation | Hindered linking agents and methods |
US4902502A (en) * | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
US5089261A (en) * | 1989-01-23 | 1992-02-18 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
US5166322A (en) * | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
DE3922089A1 (en) * | 1989-05-09 | 1990-12-13 | Basf Ag | NEW PROTEINS AND THEIR PRODUCTION |
NZ235148A (en) * | 1989-09-05 | 1991-12-23 | Immunex Corp | Tumour necrosis factor receptor protein and dna sequences |
US5605690A (en) * | 1989-09-05 | 1997-02-25 | Immunex Corporation | Methods of lowering active TNF-α levels in mammals using tumor necrosis factor receptor |
US5395760A (en) * | 1989-09-05 | 1995-03-07 | Immunex Corporation | DNA encoding tumor necrosis factor-α and -β receptors |
ATE194384T1 (en) * | 1989-09-12 | 2000-07-15 | Hoffmann La Roche | TNF-BINDING PROTEINS |
US5350836A (en) * | 1989-10-12 | 1994-09-27 | Ohio University | Growth hormone antagonists |
US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
CA2068320C (en) * | 1989-11-29 | 2000-10-17 | Robert Hageman | Production of recombinant human interleukin-1 inhibitor |
EP0464176B1 (en) † | 1990-01-23 | 1995-07-12 | MERCK PATENT GmbH | Liquid crystalline medium |
US5136021A (en) * | 1990-02-27 | 1992-08-04 | Health Research, Inc. | TNF-inhibitory protein and a method of production |
US5171264A (en) * | 1990-02-28 | 1992-12-15 | Massachusetts Institute Of Technology | Immobilized polyethylene oxide star molecules for bioapplications |
US5349053A (en) * | 1990-06-01 | 1994-09-20 | Protein Design Labs, Inc. | Chimeric ligand/immunoglobulin molecules and their uses |
ATE185601T1 (en) | 1990-07-10 | 1999-10-15 | Cambridge Antibody Tech | METHOD FOR PRODUCING SPECIFIC BONDING PAIRS |
EP0544815A1 (en) | 1990-07-17 | 1993-06-09 | The Board Of Regents Of The University Of Oklahoma | Peptides from the GMP-140 lectinbindingdomain and selectin binding ligands on carbonhydrates |
GB9022648D0 (en) * | 1990-10-18 | 1990-11-28 | Charing Cross Sunley Research | Polypeptide and its use |
US5252714A (en) * | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
WO1992016192A1 (en) * | 1991-03-15 | 1992-10-01 | Amgen Inc. | Pulmonary administration of granulocyte colony stimulating factor |
US6139843A (en) | 1991-04-02 | 2000-10-31 | Albert Einstein College Of Medicine Of Yeshiva University | Peptide compositions for the treatment of HIV |
IL99120A0 (en) * | 1991-08-07 | 1992-07-15 | Yeda Res & Dev | Multimers of the soluble forms of tnf receptors,their preparation and pharmaceutical compositions containing them |
US5376367A (en) * | 1991-11-22 | 1994-12-27 | Immunex Corporation | Fusion proteins comprising MGF and IL-3 |
US5569779A (en) * | 1991-12-23 | 1996-10-29 | Albemarle Corporation | Polyfunctional michael addition products |
ATE156158T1 (en) | 1992-04-14 | 1997-08-15 | Cornell Res Foundation Inc | MACROMOLECULES BASED ON DENDRITIC POLYMERS AND METHOD FOR THE PRODUCTION |
EP0640094A1 (en) † | 1992-04-24 | 1995-03-01 | The Board Of Regents, The University Of Texas System | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
US5792451A (en) * | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
WO1994004689A1 (en) * | 1992-08-14 | 1994-03-03 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Recombinant toxin with increased half-life |
US5382657A (en) * | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
WO1994006476A1 (en) * | 1992-09-15 | 1994-03-31 | Immunex Corporation | Method of treating tnf-dependent inflammation using tumor necrosis factor antagonists |
EP0672068A4 (en) | 1992-09-25 | 1997-02-26 | Commw Scient Ind Res Org | Target binding polypeptide. |
WO1995003827A1 (en) * | 1993-07-30 | 1995-02-09 | Kennedy Institute Of Rheumatology | Method for treating multiple sclerosis |
WO1995009917A1 (en) | 1993-10-07 | 1995-04-13 | The Regents Of The University Of California | Genetically engineered bispecific tetravalent antibodies |
US5998172A (en) † | 1993-11-02 | 1999-12-07 | Duke University | Anti-CD6 ligand antibodies |
US5446090A (en) * | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
US5981478A (en) | 1993-11-24 | 1999-11-09 | La Jolla Cancer Research Foundation | Integrin-binding peptides |
GB2285446B (en) | 1994-01-03 | 1999-07-28 | Genentech Inc | Thrombopoietin |
CA2183266A1 (en) | 1994-02-14 | 1995-08-17 | Richard D. Holly | Hematopoietic protein and materials and methods for making it |
WO1995021919A2 (en) | 1994-02-14 | 1995-08-17 | Kirin Brewery Company, Limited | Protein having tpo activity |
CZ288926B6 (en) | 1994-03-31 | 2001-09-12 | Amgen Inc. | MGDF derivative, process of its preparation and pharmaceutical preparation in it is comprised |
ES2281899T3 (en) † | 1994-05-06 | 2007-10-01 | Institut Gustave Roussy | SOLUBLE POLYPEPTIDIC FRACTIONS OF LAG-3 PROTEIN; PRODUCTION PROCEDURE; THERAPEUTIC COMPOSITION; ANTI-IDIOTIPO ANTIBODY. |
US6184205B1 (en) † | 1994-07-22 | 2001-02-06 | University Of North Carolina At Chapel Hill | GRB2 SH3 binding peptides and methods of isolating and using same |
US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
IL111196A0 (en) | 1994-10-07 | 1994-12-29 | Yeda Res & Dev | Peptides and pharmaceutical compositions comprising them |
US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
JPH10510155A (en) | 1994-12-07 | 1998-10-06 | バイオネブラスカ・インコーポレイテッド | Method for producing peptide using recombinant fusion protein construct |
JPH11501506A (en) | 1994-12-12 | 1999-02-09 | ベス イスラエル デアコネス メディカル センター | Chimeric cytokines and their use |
WO1996023899A1 (en) | 1995-02-01 | 1996-08-08 | University Of Massachusetts Medical Center | Methods of selecting a random peptide that binds to a target protein |
IL113159A0 (en) | 1995-03-28 | 1995-06-29 | Yeda Res & Dev | Synthetic peptides and pharmaceutical compositions comprising them |
US6096871A (en) * | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
YU34196A (en) | 1995-06-07 | 1999-03-04 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
NZ310778A (en) | 1995-06-07 | 1999-10-28 | Glaxo Group Ltd | Peptides and compounds that bind to a thrombopoietin receptor |
US5767078A (en) | 1995-06-07 | 1998-06-16 | Johnson; Dana L. | Agonist peptide dimers |
IL118524A (en) | 1995-06-19 | 2004-02-19 | Akzo Nobel Nv | Peptides and pharmaceutical compositions containing them useful in a peptide tolerance therapy |
US5955574A (en) † | 1995-07-13 | 1999-09-21 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A. | Analogs of parathyroid hormone |
WO1997008553A1 (en) | 1995-08-22 | 1997-03-06 | The Regents Of The University Of California | Targeting of proteins to the cell wall of gram-positive bacteria |
US5817750A (en) | 1995-08-28 | 1998-10-06 | La Jolla Cancer Research Foundation | Structural mimics of RGD-binding sites |
US6369027B1 (en) | 1995-12-22 | 2002-04-09 | Amgen Inc. | Osteoprotegerin |
US5723125A (en) * | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
IL125552A0 (en) | 1996-02-09 | 1999-03-12 | Amgen Inc | Composition comprising interleukin-1 inhibitor and controlled release polymer |
IL117223A0 (en) | 1996-02-22 | 1996-06-18 | Yeda Res & Dev | Antipathogenic polypeptides and compositions comprising them |
US5747639A (en) * | 1996-03-06 | 1998-05-05 | Amgen Boulder Inc. | Use of hydrophobic interaction chromatography to purify polyethylene glycols |
JP4046354B2 (en) | 1996-03-18 | 2008-02-13 | ボード オブ リージェンツ,ザ ユニバーシティ オブ テキサス システム | Immunoglobulin-like domain with increased half-life |
US5798246A (en) | 1996-03-25 | 1998-08-25 | Incyte Pharmaceuticals, Inc. | Cyclic nucleotide phosphodiesterase |
JP4088344B2 (en) | 1996-03-28 | 2008-05-21 | カイロン コーポレイション | Peptide ligand of urokinase receptor |
IL118003A0 (en) | 1996-04-23 | 1996-08-04 | Yeda Res & Dev | Novel vip fragments and pharmaceutical compositions comprising them |
US6100071A (en) | 1996-05-07 | 2000-08-08 | Genentech, Inc. | Receptors as novel inhibitors of vascular endothelial growth factor activity and processes for their production |
WO1997043316A1 (en) † | 1996-05-10 | 1997-11-20 | Beth Israel Deaconess Medical Center, Inc. | Physiologically active molecules with extended half-lives and methods of using same |
WO1997046668A1 (en) | 1996-06-07 | 1997-12-11 | Takeda Chemical Industries, Ltd. | Novel peptide, process for the production of the same, and use of the same |
US6126939A (en) | 1996-09-03 | 2000-10-03 | Yeda Research And Development Co. Ltd. | Anti-inflammatory dipeptide and pharmaceutical composition thereof |
DE69734887T2 (en) | 1996-09-10 | 2006-08-24 | The Burnham Institute, La Jolla | TUMOR FINDING MOLECULES, DIVIDING CONJUGATES, AND METHOD FOR USE THEREOF |
JP2001512560A (en) | 1996-10-08 | 2001-08-21 | ユー―ビスイス ベスローテン フェンノートシャップ | Methods and means for the selection of peptides and proteins with specific affinity for a target |
US5958703A (en) * | 1996-12-03 | 1999-09-28 | Glaxo Group Limited | Use of modified tethers in screening compound libraries |
EP2002846B1 (en) | 1996-12-06 | 2017-01-25 | Amgen Inc. | Combination therapy using an IL-1 inhibitor for treating IL-1 mediated diseases |
HU227088B1 (en) | 1996-12-20 | 2010-06-28 | Amgen Inc | Ob fusion protein compositions and process for producing thereof |
KR19980066046A (en) | 1997-01-18 | 1998-10-15 | 정용훈 | High-CTLA4-Ig fusion protein |
WO1998033812A1 (en) | 1997-02-05 | 1998-08-06 | Brigham And Women's Hospital, Inc. | Mast cell protease peptide inhibitors |
JP4086908B2 (en) | 1997-04-17 | 2008-05-14 | アムジエン・インコーポレーテツド | Compositions and methods comprising conjugates of stable and active human OB protein and antibody Fc chains |
US6265535B1 (en) | 1997-05-30 | 2001-07-24 | The Trustees Of The University Of Pennsylvania | Peptides and peptide analogues designed from binding sites of tumor necrosis factor receptor superfamily and their uses |
JP2002504818A (en) | 1997-06-06 | 2002-02-12 | リジェネロン ファーマシューティカルズ,インコーポレイテッド | NTN-2 members of the ligand family |
WO1999005302A1 (en) | 1997-07-24 | 1999-02-04 | The Perkin-Elmer Corporation | Conjugates of transporter peptides and nucleic acid analogs, and their use |
US6238667B1 (en) | 1997-09-19 | 2001-05-29 | Heinz Kohler | Method of affinity cross-linking biologically active immunogenic peptides to antibodies |
WO1999018243A1 (en) | 1997-10-06 | 1999-04-15 | Millennium Pharmaceuticals, Inc. | Signal peptide containing proteins and uses therefor |
WO1999018781A1 (en) | 1997-10-10 | 1999-04-22 | Cytovia, Inc. | Dipeptide apoptosis inhibitors and the use thereof |
DE69812727D1 (en) | 1997-11-07 | 2003-04-30 | Conjuchem Inc | Opioid conjugates with endogenous carrier proteins |
CA2341029A1 (en) | 1998-08-17 | 2000-02-24 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
EP1135153B1 (en) * | 1998-11-20 | 2005-04-27 | Genentech, Inc. | Uses for eph receptor antagonists and agonists to treat vascular disorders |
WO2000047740A2 (en) * | 1999-02-12 | 2000-08-17 | Amgen Inc. | Tnf-related proteins |
ATE330967T1 (en) † | 1999-07-02 | 2006-07-15 | Genentech Inc | PEPTIDE COMPOUNDS BINDING TO HER2 |
IL147270A0 (en) † | 1999-07-02 | 2002-08-14 | Genentech Inc | Fusion peptides comprising a peptide ligand domain and a multimerization domain |
US20020160416A1 (en) * | 2000-02-11 | 2002-10-31 | Boyle William J. | Receptor from TNF family |
US7658924B2 (en) * | 2001-10-11 | 2010-02-09 | Amgen Inc. | Angiopoietin-2 specific binding agents |
US7138370B2 (en) * | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
US7521053B2 (en) * | 2001-10-11 | 2009-04-21 | Amgen Inc. | Angiopoietin-2 specific binding agents |
BR0312276A (en) | 2002-06-28 | 2005-04-26 | Centocor Inc | Mammalian epo ch1-removed mimetibodies, compositions, methods and uses |
WO2004002417A2 (en) | 2002-06-28 | 2004-01-08 | Centocor, Inc. | Mammalian ch1 deleted mimetibodies, compositions, methods and uses |
US20070280947A1 (en) * | 2004-06-25 | 2007-12-06 | Licentia, Ltd. | Tie Receptor and Tie Ligand Materials and Methods for Modulating Female Fertility |
AU2005319382B2 (en) * | 2004-12-21 | 2011-04-07 | Astrazeneca Ab | Antibodies directed to angiopoietin-2 and uses thereof |
-
1999
- 1999-10-22 US US09/428,082 patent/US6660843B1/en not_active Expired - Lifetime
- 1999-10-25 AU AU12322/00A patent/AU767725B2/en not_active Ceased
- 1999-10-25 MX MXPA01003873A patent/MXPA01003873A/en not_active IP Right Cessation
- 1999-10-25 BR BR9914708-4A patent/BR9914708A/en not_active IP Right Cessation
- 1999-10-25 EA EA200100464A patent/EA005404B1/en not_active IP Right Cessation
- 1999-10-25 CN CNA2005100814960A patent/CN1781946A/en active Pending
- 1999-10-25 KR KR1020077006961A patent/KR100753305B1/en not_active IP Right Cessation
- 1999-10-25 CN CNB2005100814956A patent/CN100384879C/en not_active Expired - Lifetime
- 1999-10-25 DK DK99971003.1T patent/DK1144454T4/en active
- 1999-10-25 NZ NZ510888A patent/NZ510888A/en not_active IP Right Cessation
- 1999-10-25 SK SK525-2001A patent/SK287037B6/en not_active IP Right Cessation
- 1999-10-25 WO PCT/US1999/025044 patent/WO2000024782A2/en active IP Right Grant
- 1999-10-25 CN CNA2005100825912A patent/CN1721447A/en active Pending
- 1999-10-25 CN CNA2005100836974A patent/CN1746190A/en active Pending
- 1999-10-25 CA CA2347131A patent/CA2347131C/en not_active Expired - Lifetime
- 1999-10-25 PT PT99971003T patent/PT1144454E/en unknown
- 1999-10-25 DE DE69937752T patent/DE69937752T3/en not_active Expired - Lifetime
- 1999-10-25 IL IL14236599A patent/IL142365A0/en unknown
- 1999-10-25 CZ CZ2001-1323A patent/CZ304242B6/en not_active IP Right Cessation
- 1999-10-25 CN CNB998147273A patent/CN1310948C/en not_active Expired - Fee Related
- 1999-10-25 KR KR1020077006958A patent/KR100753304B1/en active IP Right Grant
- 1999-10-25 CN CNB200510083696XA patent/CN100384880C/en not_active Expired - Fee Related
- 1999-10-25 CN CNA2005100819521A patent/CN1908014A/en active Pending
- 1999-10-25 EP EP99971003A patent/EP1144454B2/en not_active Expired - Lifetime
- 1999-10-25 HU HU0203506A patent/HU229485B1/en unknown
- 1999-10-25 RS YU25901A patent/RS51852B/en unknown
- 1999-10-25 PL PL366080A patent/PL211164B1/en not_active IP Right Cessation
- 1999-10-25 ES ES99971003T patent/ES2299278T5/en not_active Expired - Lifetime
- 1999-10-25 KR KR1020017004982A patent/KR100753303B1/en not_active IP Right Cessation
- 1999-10-25 CN CNA2005100814975A patent/CN1781947A/en active Pending
- 1999-10-25 NZ NZ528882A patent/NZ528882A/en not_active IP Right Cessation
- 1999-10-25 SI SI9930999T patent/SI1144454T2/en unknown
- 1999-10-25 JP JP2000578351A patent/JP2003512011A/en not_active Withdrawn
- 1999-10-25 AT AT99971003T patent/ATE380828T1/en active
-
2001
- 2001-04-02 IL IL142365A patent/IL142365A/en not_active IP Right Cessation
- 2001-04-04 ZA ZA200102753A patent/ZA200102753B/en unknown
- 2001-04-20 NO NO20011963A patent/NO331733B1/en not_active IP Right Cessation
- 2001-04-24 BG BG105461A patent/BG65721B1/en unknown
-
2002
- 2002-04-10 HK HK02102701.4A patent/HK1042097B/en not_active IP Right Cessation
-
2003
- 2003-06-27 US US10/609,217 patent/US7166707B2/en not_active Expired - Fee Related
- 2003-07-31 US US10/632,388 patent/US7189827B2/en not_active Expired - Lifetime
- 2003-08-18 US US10/645,761 patent/US20040071712A1/en not_active Abandoned
- 2003-08-29 US US10/653,048 patent/US7186810B2/en not_active Expired - Fee Related
- 2003-08-29 US US10/651,723 patent/US7169905B2/en not_active Expired - Fee Related
-
2004
- 2004-02-20 AU AU2004200687A patent/AU2004200687C1/en not_active Ceased
- 2004-02-20 AU AU2004200690A patent/AU2004200690C1/en not_active Ceased
-
2006
- 2006-10-23 HK HK06111669A patent/HK1090932A1/en not_active IP Right Cessation
- 2006-10-24 JP JP2006288397A patent/JP2007084558A/en not_active Withdrawn
- 2006-10-24 JP JP2006288347A patent/JP2007091747A/en active Pending
- 2006-10-24 JP JP2006288398A patent/JP2007105044A/en active Pending
- 2006-10-24 JP JP2006288324A patent/JP2007091746A/en not_active Withdrawn
- 2006-10-24 JP JP2006288325A patent/JP2007084555A/en not_active Withdrawn
- 2006-10-24 JP JP2006288382A patent/JP2007089586A/en active Pending
- 2006-10-24 JP JP2006288383A patent/JP2007084557A/en not_active Withdrawn
- 2006-10-24 JP JP2006288346A patent/JP2007084556A/en active Pending
- 2006-10-31 US US11/591,002 patent/US20070049532A1/en not_active Abandoned
-
2008
- 2008-02-11 CY CY20081100156T patent/CY1107881T1/en unknown
Patent Citations (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5985599A (en) * | 1986-05-29 | 1999-11-16 | The Austin Research Institute | FC receptor for immunoglobulin |
US5336603A (en) * | 1987-10-02 | 1994-08-09 | Genentech, Inc. | CD4 adheson variants |
US6117655A (en) * | 1987-10-02 | 2000-09-12 | Genentech, Inc. | Nucleic acid encoding adhesion variants |
US5223409A (en) * | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
US5726290A (en) * | 1988-12-22 | 1998-03-10 | Genentech, Inc. | Soluble analogues of integrins |
US5225538A (en) * | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
US5714147A (en) * | 1989-02-23 | 1998-02-03 | Genentech Inc. | Hybrid immunoglobulins |
US5216131A (en) * | 1989-02-23 | 1993-06-01 | Genentech, Inc. | Lymphocyte homing receptors |
US5428130A (en) * | 1989-02-23 | 1995-06-27 | Genentech, Inc. | Hybrid immunoglobulins |
US5098833A (en) * | 1989-02-23 | 1992-03-24 | Genentech, Inc. | DNA sequence encoding a functional domain of a lymphocyte homing receptor |
US5455165A (en) * | 1989-02-23 | 1995-10-03 | Genentech, Inc. | Expression vector encoding hybrid immunoglobulins |
US5116964A (en) * | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
US5514582A (en) * | 1989-02-23 | 1996-05-07 | Genentech, Inc. | Recombinant DNA encoding hybrid immunoglobulins |
US5840844A (en) * | 1989-02-23 | 1998-11-24 | Genentech, Inc. University Of California | Soluble lymphocyte homing receptors |
US5877151A (en) * | 1989-07-05 | 1999-03-02 | The Board Of Regents Of The University Of Oklahoma | Method for inhibiting production of tumor necrosis factor |
US5432018A (en) * | 1990-06-20 | 1995-07-11 | Affymax Technologies N.V. | Peptide library and screening systems |
US5733731A (en) * | 1991-10-16 | 1998-03-31 | Affymax Technologies N.V. | Peptide library and screening method |
US5338665A (en) * | 1991-10-16 | 1994-08-16 | Affymax Technologies N.V. | Peptide library and screening method |
US5498530A (en) * | 1991-10-16 | 1996-03-12 | Affymax Technologies, N.V. | Peptide library and screening method |
US5480981A (en) * | 1992-05-26 | 1996-01-02 | Immunex Corporation | CD30 ligand |
US5556335A (en) * | 1993-03-23 | 1996-09-17 | Holyoake Industries Limited | Thermally controlled diffusers |
US5922545A (en) * | 1993-10-29 | 1999-07-13 | Affymax Technologies N.V. | In vitro peptide and antibody display libraries |
US5773569A (en) * | 1993-11-19 | 1998-06-30 | Affymax Technologies N.V. | Compounds and peptides that bind to the erythropoietin receptor |
US5767234A (en) * | 1994-02-02 | 1998-06-16 | Affymax Technologies, N.V. | Peptides and compounds that bind to the IL-1 receptor |
US5786331A (en) * | 1994-02-02 | 1998-07-28 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
US5608035A (en) * | 1994-02-02 | 1997-03-04 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
US5880096A (en) * | 1994-02-02 | 1999-03-09 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
US5869452A (en) * | 1994-11-10 | 1999-02-09 | Monash University | Treatment of obesity |
US5739277A (en) * | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
US5869451A (en) * | 1995-06-07 | 1999-02-09 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
US5932546A (en) * | 1996-10-04 | 1999-08-03 | Glaxo Wellcome Inc. | Peptides and compounds that bind to the thrombopoietin receptor |
US6919426B2 (en) * | 2002-09-19 | 2005-07-19 | Amgen Inc. | Peptides and related molecules that modulate nerve growth factor activity |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090202619A1 (en) * | 2005-02-18 | 2009-08-13 | The University Of Tokushima | Polyoxyalkylene chain-containing lipid derivative and lipid film structure containing such derivative |
US20070134234A1 (en) * | 2005-09-29 | 2007-06-14 | Viral Logic Systems Technology Corp. | Immunomodulatory compositions and uses therefor |
EP2275816A2 (en) | 2006-03-22 | 2011-01-19 | Viral Logic Systems Technology Corp. | Methods for identifying polypeptide targets and uses thereof for treating immunological diseases |
EP2322931A2 (en) | 2006-03-22 | 2011-05-18 | Viral Logic Systems Technology Corp. | Methods for identifying polypeptide targets and uses thereof for treating immunological diseases |
US9283260B2 (en) | 2006-04-21 | 2016-03-15 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
US10166189B2 (en) | 2006-04-21 | 2019-01-01 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
US20080131431A1 (en) * | 2006-05-15 | 2008-06-05 | Viral Logic Systems Technology Corp. | CD47 related compositions and methods for treating immunological diseases and disorders |
US20100239579A1 (en) * | 2006-05-15 | 2010-09-23 | Viral Logic Systems Technology Corp. | CD47 Related Compositions and Methods for Treating Immunological Diseases and Disorders |
US8377448B2 (en) | 2006-05-15 | 2013-02-19 | The Board Of Trustees Of The Leland Standford Junior University | CD47 related compositions and methods for treating immunological diseases and disorders |
WO2015057820A3 (en) * | 2013-10-15 | 2015-06-18 | Roberts S Kenny | Peptide constructs and well-defined aggregates thereof |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1144454B1 (en) | Modified peptides as therapeutic agents | |
US20040077022A1 (en) | Modified peptides as therapeutic agents | |
AU2001259432B2 (en) | Modified peptides, comprising an FC domain, as therapeutic agents | |
AU2001259432A1 (en) | Modified peptides, comprising an Fc domain, as therapeutic agents | |
AU2004200691B2 (en) | Modified peptides as therapeutic agents | |
AU2004231208A1 (en) | Modified peptides as therapeutic agents |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |