WO1999055718A2 - Solution phase biopolymer synthesis - Google Patents
Solution phase biopolymer synthesis Download PDFInfo
- Publication number
- WO1999055718A2 WO1999055718A2 PCT/US1999/008939 US9908939W WO9955718A2 WO 1999055718 A2 WO1999055718 A2 WO 1999055718A2 US 9908939 W US9908939 W US 9908939W WO 9955718 A2 WO9955718 A2 WO 9955718A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lpc
- aryl
- tris
- diaza
- alkyl
- Prior art date
Links
- 229920001222 biopolymer Polymers 0.000 title claims abstract description 113
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 101
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 98
- 238000000034 method Methods 0.000 claims abstract description 92
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 29
- 239000007791 liquid phase Substances 0.000 claims abstract description 13
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 12
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 11
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 7
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 7
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 7
- 102000004169 proteins and genes Human genes 0.000 claims abstract 2
- 108090000623 proteins and genes Proteins 0.000 claims abstract 2
- -1 nitro, formyl Chemical group 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 93
- 125000003118 aryl group Chemical group 0.000 claims description 89
- 125000001072 heteroaryl group Chemical group 0.000 claims description 73
- 125000002577 pseudohalo group Chemical group 0.000 claims description 65
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 46
- 239000000178 monomer Substances 0.000 claims description 45
- 125000002947 alkylene group Chemical group 0.000 claims description 43
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 42
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
- 239000000243 solution Substances 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 30
- 125000004122 cyclic group Chemical group 0.000 claims description 27
- 239000007983 Tris buffer Substances 0.000 claims description 23
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 23
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 23
- 108091093037 Peptide nucleic acid Proteins 0.000 claims description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 22
- QMKYBPDZANOJGF-UHFFFAOYSA-N benzene-1,3,5-tricarboxylic acid Chemical compound OC(=O)C1=CC(C(O)=O)=CC(C(O)=O)=C1 QMKYBPDZANOJGF-UHFFFAOYSA-N 0.000 claims description 21
- 150000008300 phosphoramidites Chemical class 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 17
- 239000000539 dimer Substances 0.000 claims description 16
- 125000001188 haloalkyl group Chemical group 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000000732 arylene group Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- 239000013638 trimer Substances 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 125000004450 alkenylene group Chemical group 0.000 claims description 12
- 125000004419 alkynylene group Chemical group 0.000 claims description 12
- 125000005647 linker group Chemical group 0.000 claims description 12
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 12
- 239000012071 phase Substances 0.000 claims description 12
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 150000002825 nitriles Chemical group 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 9
- 125000005110 aryl thio group Chemical group 0.000 claims description 9
- 125000001118 alkylidene group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 150000001413 amino acids Chemical class 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 239000002773 nucleotide Substances 0.000 claims description 8
- 125000003729 nucleotide group Chemical group 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 7
- 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 7
- 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims description 7
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 7
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 7
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 7
- 239000002777 nucleoside Substances 0.000 claims description 7
- 229920001774 Perfluoroether Polymers 0.000 claims description 6
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 6
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 6
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000005128 aryl amino alkyl group Chemical group 0.000 claims description 6
- 125000001769 aryl amino group Chemical group 0.000 claims description 6
- 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 6
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 6
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 6
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 6
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 6
- 125000004986 diarylamino group Chemical group 0.000 claims description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 6
- 125000006684 polyhaloalkyl group Chemical group 0.000 claims description 6
- 125000005031 thiocyano group Chemical group S(C#N)* 0.000 claims description 6
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
- 125000005162 aryl oxy carbonyl amino group Chemical group 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- 125000003835 nucleoside group Chemical group 0.000 claims description 5
- 125000005549 heteroarylene group Chemical group 0.000 claims description 4
- 150000002772 monosaccharides Chemical class 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- OFKUAGPTUWMPSX-UHFFFAOYSA-N n-(2-aminoethyl)-3-[3-[3-(2-aminoethylamino)-3-oxopropoxy]-2,2-bis[[3-(2-aminoethylamino)-3-oxopropoxy]methyl]propoxy]propanamide Chemical compound NCCNC(=O)CCOCC(COCCC(=O)NCCN)(COCCC(=O)NCCN)COCCC(=O)NCCN OFKUAGPTUWMPSX-UHFFFAOYSA-N 0.000 claims description 3
- LMDLEWFKFNESMM-UHFFFAOYSA-N 4-[2-[bis[2-(3-carboxypropanoylamino)ethyl]amino]ethylamino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NCCN(CCNC(=O)CCC(O)=O)CCNC(=O)CCC(O)=O LMDLEWFKFNESMM-UHFFFAOYSA-N 0.000 claims description 2
- BJVRDWSCILKKCD-UHFFFAOYSA-N 3-[2-[3-[3-[3-[2-[(2-carboxyacetyl)amino]ethylamino]-3-oxopropoxy]-2,2-bis[[3-[2-[(2-carboxyacetyl)amino]ethylamino]-3-oxopropoxy]methyl]propoxy]propanoylamino]ethylamino]-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)NCCNC(=O)CCOCC(COCCC(=O)NCCNC(=O)CC(O)=O)(COCCC(=O)NCCNC(=O)CC(O)=O)COCCC(=O)NCCNC(=O)CC(O)=O BJVRDWSCILKKCD-UHFFFAOYSA-N 0.000 claims 1
- 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 abstract description 17
- 238000002360 preparation method Methods 0.000 abstract description 12
- 239000000969 carrier Substances 0.000 abstract description 11
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 9
- 125000000524 functional group Chemical group 0.000 abstract description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 1
- 150000004820 halides Chemical class 0.000 description 79
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 38
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 150000002148 esters Chemical class 0.000 description 25
- 239000000047 product Substances 0.000 description 25
- 238000005227 gel permeation chromatography Methods 0.000 description 22
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 22
- 238000000746 purification Methods 0.000 description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 229910019142 PO4 Inorganic materials 0.000 description 18
- 235000021317 phosphate Nutrition 0.000 description 18
- 239000003480 eluent Substances 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000002843 carboxylic acid group Chemical group 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 150000001266 acyl halides Chemical class 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 14
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical class C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 14
- 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 14
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 13
- 150000001262 acyl bromides Chemical class 0.000 description 13
- 150000001263 acyl chlorides Chemical class 0.000 description 13
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 13
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical class [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 13
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 13
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 13
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 13
- 150000003003 phosphines Chemical class 0.000 description 13
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 13
- 150000003871 sulfonates Chemical class 0.000 description 13
- 150000003457 sulfones Chemical class 0.000 description 13
- 150000003462 sulfoxides Chemical class 0.000 description 13
- 150000003463 sulfur Chemical class 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 125000004149 thio group Chemical group *S* 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 238000002515 oligonucleotide synthesis Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- UBTJZUKVKGZHAD-UPRLRBBYSA-N 1-[(2r,4s,5r)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](O)C[C@H](N2C(NC(=O)C(C)=C2)=O)O1 UBTJZUKVKGZHAD-UPRLRBBYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 238000010549 co-Evaporation Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 238000010532 solid phase synthesis reaction Methods 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 6
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 6
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 238000006386 neutralization reaction Methods 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 0 **c1cc(**)cc([*-])c1 Chemical compound **c1cc(**)cc([*-])c1 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 239000005864 Sulphur Substances 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- MIUOBAHGBPSRKY-UHFFFAOYSA-N 5-(4-nitrophenyl)-2h-tetrazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NNN=N1 MIUOBAHGBPSRKY-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000006136 alcoholysis reaction Methods 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 150000004662 dithiols Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 description 3
- GRODQBWIKNJXFJ-UHFFFAOYSA-N 1,1-dimethoxy-2,2,2-triphenylethanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(O)(OC)OC)C1=CC=CC=C1 GRODQBWIKNJXFJ-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-BIIVOSGPSA-N 2'-deoxythymidine Natural products O=C1NC(=O)C(C)=CN1[C@@H]1O[C@@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-BIIVOSGPSA-N 0.000 description 2
- KSXHZOTTWSNEHY-UHFFFAOYSA-N 3-[3-(2-cyanoethoxy)-2,2-bis(2-cyanoethoxymethyl)propoxy]propanenitrile Chemical compound N#CCCOCC(COCCC#N)(COCCC#N)COCCC#N KSXHZOTTWSNEHY-UHFFFAOYSA-N 0.000 description 2
- BRARRAHGNDUELT-UHFFFAOYSA-N 3-hydroxypicolinic acid Chemical compound OC(=O)C1=NC=CC=C1O BRARRAHGNDUELT-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000007098 aminolysis reaction Methods 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 125000001743 benzylic group Chemical group 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 230000027832 depurination Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- XTAZYLNFDRKIHJ-UHFFFAOYSA-N n,n-dioctyloctan-1-amine Chemical compound CCCCCCCCN(CCCCCCCC)CCCCCCCC XTAZYLNFDRKIHJ-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 150000007970 thio esters Chemical class 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- RGCHNYAILFZUPL-UHFFFAOYSA-N trimethyl benzene-1,3,5-tricarboxylate Chemical compound COC(=O)C1=CC(C(=O)OC)=CC(C(=O)OC)=C1 RGCHNYAILFZUPL-UHFFFAOYSA-N 0.000 description 2
- 239000011800 void material Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- PJKMOHIGRNELRP-UHFFFAOYSA-N 1,3,5-tris(chloromethyl)benzene Chemical compound ClCC1=CC(CCl)=CC(CCl)=C1 PJKMOHIGRNELRP-UHFFFAOYSA-N 0.000 description 1
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
- JPSKCQCQZUGWNM-UHFFFAOYSA-N 2,7-Oxepanedione Chemical compound O=C1CCCCC(=O)O1 JPSKCQCQZUGWNM-UHFFFAOYSA-N 0.000 description 1
- BCYIUCVPTJDUPV-UHFFFAOYSA-N 2-(2-nitrophenyl)propanoic acid Chemical class OC(=O)C(C)C1=CC=CC=C1[N+]([O-])=O BCYIUCVPTJDUPV-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- MGMNPSAERQZUIM-UHFFFAOYSA-N 2-(hydroxymethyl)benzoic acid Chemical class OCC1=CC=CC=C1C(O)=O MGMNPSAERQZUIM-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical group O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- KMEMIMRPZGDOMG-UHFFFAOYSA-N 2-cyanoethoxyphosphonamidous acid Chemical class NP(O)OCCC#N KMEMIMRPZGDOMG-UHFFFAOYSA-N 0.000 description 1
- VKIGAWAEXPTIOL-UHFFFAOYSA-N 2-hydroxyhexanenitrile Chemical compound CCCCC(O)C#N VKIGAWAEXPTIOL-UHFFFAOYSA-N 0.000 description 1
- GHPQJPRAZGODJV-UHFFFAOYSA-N 3-[3-(2-cyanoethoxy)-2,2-bis(2-cyanoethoxymethyl)propoxy]propanenitrile;methyl 3-[3-(3-methoxy-3-oxopropoxy)-2,2-bis[(3-methoxy-3-oxopropoxy)methyl]propoxy]propanoate Chemical compound N#CCCOCC(COCCC#N)(COCCC#N)COCCC#N.COC(=O)CCOCC(COCCC(=O)OC)(COCCC(=O)OC)COCCC(=O)OC GHPQJPRAZGODJV-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 1
- JGLHXBNHKQAROV-UHFFFAOYSA-N 9-methoxy-9h-fluorene Chemical group C1=CC=C2C(OC)C3=CC=CC=C3C2=C1 JGLHXBNHKQAROV-UHFFFAOYSA-N 0.000 description 1
- NAXKFVIRJICPAO-LHNWDKRHSA-N Allin Natural products OC[C@H]1O[C@H]2O[C@H]3[C@H](CO)O[C@H](O[C@H]4[C@H](CO)O[C@H](O[C@@H]5[C@@H](CO)O[C@H](O[C@H]6[C@H](CO)O[C@H](O[C@H]7[C@H](CO)O[C@@H](O[C@H]8[C@H](CO)O[C@@H](O[C@@H]1[C@@H]1S[C@@H]21)[C@@H]1S[C@H]81)[C@H]1S[C@@H]71)[C@H]1S[C@H]61)[C@H]1S[C@@H]51)[C@H]1S[C@@H]41)[C@H]1S[C@H]31 NAXKFVIRJICPAO-LHNWDKRHSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 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
- 229910014033 C-OH Inorganic materials 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- IVSZLXZYQVIEFR-UHFFFAOYSA-N Cc1cc(C)ccc1 Chemical compound Cc1cc(C)ccc1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 102000006471 Fucosyltransferases Human genes 0.000 description 1
- 108010019236 Fucosyltransferases Proteins 0.000 description 1
- 102000030902 Galactosyltransferase Human genes 0.000 description 1
- 108060003306 Galactosyltransferase Proteins 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 102000051366 Glycosyltransferases Human genes 0.000 description 1
- 108700023372 Glycosyltransferases Proteins 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- NVGBPTNZLWRQSY-UWVGGRQHSA-N Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN NVGBPTNZLWRQSY-UWVGGRQHSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 101100379142 Mus musculus Anxa1 gene Proteins 0.000 description 1
- 229910003849 O-Si Inorganic materials 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- RVQDZELMXZRSSI-IUCAKERBSA-N Pro-Lys Chemical group NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 RVQDZELMXZRSSI-IUCAKERBSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical group 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine group Chemical group [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C=NC=2C(N)=NC=NC12 OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- PPQRONHOSHZGFQ-LMVFSUKVSA-N aldehydo-D-ribose 5-phosphate Chemical group OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PPQRONHOSHZGFQ-LMVFSUKVSA-N 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 108010068380 arginylarginine Proteins 0.000 description 1
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 150000004887 dithianes Chemical group 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 108700014210 glycosyltransferase activity proteins Proteins 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- LDXVORZMYYUSPF-UHFFFAOYSA-N hydroxymethyl 2-phenoxyacetate Chemical class OCOC(=O)COC1=CC=CC=C1 LDXVORZMYYUSPF-UHFFFAOYSA-N 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- NBZBKCUXIYYUSX-UHFFFAOYSA-N iminodiacetic acid Chemical class OC(=O)CNCC(O)=O NBZBKCUXIYYUSX-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005524 levulinyl group Chemical group 0.000 description 1
- 238000003819 low-pressure liquid chromatography Methods 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- 229940057952 methanol Drugs 0.000 description 1
- NLEUMYGLBBOTIA-UHFFFAOYSA-N methyl 3-[3-(3-methoxy-3-oxopropoxy)-2,2-bis[(3-methoxy-3-oxopropoxy)methyl]propoxy]propanoate Chemical compound COC(=O)CCOCC(COCCC(=O)OC)(COCCC(=O)OC)COCCC(=O)OC NLEUMYGLBBOTIA-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- NWKYZYGOSPOKDY-UHFFFAOYSA-N n,n-dimethylformamide;pyridine Chemical compound CN(C)C=O.C1=CC=NC=C1 NWKYZYGOSPOKDY-UHFFFAOYSA-N 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- CPGRMGOILBSUQC-UHFFFAOYSA-N phosphoryl azide Chemical compound [N-]=[N+]=NP(=O)(N=[N+]=[N-])N=[N+]=[N-] CPGRMGOILBSUQC-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- CRDYSYOERSZTHZ-UHFFFAOYSA-M selenocyanate Chemical compound [Se-]C#N CRDYSYOERSZTHZ-UHFFFAOYSA-M 0.000 description 1
- 150000004756 silanes Chemical group 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/14—Amines containing amino groups bound to at least two aminoalkyl groups, e.g. diethylenetriamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/77—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/78—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/10—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
- C07C25/18—Polycyclic aromatic halogenated hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/16—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same carbon atom of an acyclic carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/708—Ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
- C07K14/003—Peptide-nucleic acids (PNAs)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S585/00—Chemistry of hydrocarbon compounds
- Y10S585/929—Special chemical considerations
- Y10S585/93—Process including synthesis of nonhydrocarbon intermediate
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S585/00—Chemistry of hydrocarbon compounds
- Y10S585/929—Special chemical considerations
- Y10S585/93—Process including synthesis of nonhydrocarbon intermediate
- Y10S585/932—Carboxyl-containing, e.g. acid
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S585/00—Chemistry of hydrocarbon compounds
- Y10S585/929—Special chemical considerations
- Y10S585/93—Process including synthesis of nonhydrocarbon intermediate
- Y10S585/933—N-containing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S585/00—Chemistry of hydrocarbon compounds
- Y10S585/929—Special chemical considerations
- Y10S585/93—Process including synthesis of nonhydrocarbon intermediate
- Y10S585/934—Chalcogen-containing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S585/00—Chemistry of hydrocarbon compounds
- Y10S585/929—Special chemical considerations
- Y10S585/93—Process including synthesis of nonhydrocarbon intermediate
- Y10S585/935—Halogen-containing
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU36643/99A AU3664399A (en) | 1998-04-27 | 1999-04-26 | Solution phase biopolymer synthesis |
EP99918819A EP1073668A2 (en) | 1998-04-27 | 1999-04-26 | Solution phase biopolymer synthesis |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/067,337 | 1998-04-27 | ||
US09/067,337 US7094943B2 (en) | 1998-04-27 | 1998-04-27 | Solution phase biopolymer synthesis |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1999055718A2 true WO1999055718A2 (en) | 1999-11-04 |
WO1999055718A3 WO1999055718A3 (en) | 1999-12-16 |
Family
ID=22075335
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1999/008939 WO1999055718A2 (en) | 1998-04-27 | 1999-04-26 | Solution phase biopolymer synthesis |
Country Status (4)
Country | Link |
---|---|
US (2) | US7094943B2 (en) |
EP (1) | EP1073668A2 (en) |
AU (1) | AU3664399A (en) |
WO (1) | WO1999055718A2 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7038103B2 (en) | 1998-04-27 | 2006-05-02 | Hubert Koster | Solution phase biopolymer synthesis |
JP2010275254A (en) * | 2009-05-29 | 2010-12-09 | Tokyo Univ Of Agriculture & Technology | Hydrophobic group-linked nucleoside, hydrophobic group-linked nucleoside solution and method of synthesizing hydrophobic group-linked oligonucleotide |
WO2013179412A1 (en) * | 2012-05-30 | 2013-12-05 | 北海道システム・サイエンス株式会社 | Oligonucleotide synthesis method using highly dispersible liquid-phase support |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5605798A (en) * | 1993-01-07 | 1997-02-25 | Sequenom, Inc. | DNA diagnostic based on mass spectrometry |
US20060264608A1 (en) * | 2001-08-03 | 2006-11-23 | Wender Paul A | Bi-directional synthesis of oligoguanidine transport agents |
JP4741458B2 (en) | 2003-01-16 | 2011-08-03 | カプロテック・バイオアナリティクス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Method for analyzing capture compounds, collections thereof, and proteomes and composite compositions |
EP2394175B1 (en) * | 2009-02-09 | 2016-02-03 | caprotec bioanalytics GmbH | Devices, systems and methods for separating magnetic particles |
EP2971166B1 (en) | 2013-03-14 | 2021-05-19 | Children's Medical Center Corporation | Psap peptide for treating cd36 expressing cancers |
CA2943802A1 (en) | 2014-03-26 | 2015-10-01 | Children's Medical Center Corporation | Cyclic prosaposin peptides and uses thereof |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1984001779A1 (en) * | 1982-10-28 | 1984-05-10 | Hubert Koester | Process for the production of oligonucleotides |
EP0642798A2 (en) * | 1993-09-08 | 1995-03-15 | La Jolla Pharmaceutical Company | Chemically-defined non-polymeric valency platform molecules and conjugates thereof |
WO1996003148A1 (en) * | 1994-07-27 | 1996-02-08 | Ono Pharmaceutical Co., Ltd. | Method and drug for treating diabetes |
WO1997014706A1 (en) * | 1995-10-19 | 1997-04-24 | Nexstar Pharmaceuticals, Inc. | Method for solution phase synthesis of oligonucleotides |
WO1999010362A1 (en) * | 1997-08-27 | 1999-03-04 | Isis Innovation Limited | Branched dendrimeric structures |
Family Cites Families (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5198540A (en) * | 1982-10-28 | 1993-03-30 | Hubert Koster | Process for the preparation of oligonucleotides in solution |
US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
GB8518144D0 (en) | 1985-07-18 | 1985-08-21 | Univ Belfast | Solid phase peptide synthesis |
US5037882A (en) | 1987-03-11 | 1991-08-06 | Steel Samuel L | Synthesis of oligonucleotide analogs |
US4794150A (en) | 1987-03-11 | 1988-12-27 | Samuel Steel | Synthesis of peptide analogs |
SE466403B (en) | 1988-03-24 | 1992-02-10 | Kurt G I Nilsson | SAID TO SYNTHETIZE Oligosaccharides |
US5266684A (en) | 1988-05-02 | 1993-11-30 | The Reagents Of The University Of California | Peptide mixtures |
DE68921982T4 (en) | 1988-06-14 | 1996-04-25 | Cetus Oncology Corp | COUPLING AGENTS AND STERICALLY DISABLED CONJUGATES THEREOF. |
US5049656A (en) | 1988-12-21 | 1991-09-17 | Board Of Regents Of The University Of Nebraska | Sequential peptide and oligonucleotide syntheses using immunoaffinity techniques |
US5077210A (en) | 1989-01-13 | 1991-12-31 | Eigler Frances S | Immobilization of active agents on substrates with a silane and heterobifunctional crosslinking agent |
US5221754A (en) | 1989-06-09 | 1993-06-22 | Research Corporation Technologies, Inc. | Reagents for rapid peptide synthesis |
SE8902842D0 (en) | 1989-08-28 | 1989-08-28 | Pharmacia Ab | A METHOD FOR MONITORING IN PEPTIDE SYNTHESIS |
US5635488A (en) | 1991-10-15 | 1997-06-03 | Isis Pharmaceuticals, Inc. | Compounds having phosphorodithioate linkages of high chiral purity |
US5583042A (en) | 1990-04-16 | 1996-12-10 | Neose Pharmaceuticals, Inc. | Apparatus for the synthesis of saccharide compositions |
US5180674A (en) | 1990-04-16 | 1993-01-19 | The Trustees Of The University Of Pennsylvania | Saccharide compositions, methods and apparatus for their synthesis |
US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
US5648462A (en) | 1990-10-09 | 1997-07-15 | Setsuko Funakoshi | Peptide purification method using novel linker and solid-phase ligand |
US5492821A (en) | 1990-11-14 | 1996-02-20 | Cargill, Inc. | Stabilized polyacrylic saccharide protein conjugates |
EP0562025B1 (en) | 1990-12-06 | 2001-02-07 | Affymetrix, Inc. (a Delaware Corporation) | Compounds and their use in a binary synthesis strategy |
US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
US5374655A (en) | 1991-06-10 | 1994-12-20 | Alberta Research Council | Methods for the synthesis of monofucosylated oligosaccharides terminating in di-N-acetyllactosaminyl structures |
SE9102292L (en) | 1991-08-06 | 1993-02-07 | Kurt G I Nilsson | ENZYMATIC METHOD |
US5700922A (en) | 1991-12-24 | 1997-12-23 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
GB9207381D0 (en) | 1992-04-03 | 1992-05-13 | Ici Plc | Synthesis of oligonucleotides |
US5616700A (en) | 1992-04-24 | 1997-04-01 | Beckman Instruments, Inc. | Processes for synthesizing nucleotides and modified nucleotides using N.sub. |
CA2145407C (en) | 1992-09-28 | 2009-09-22 | Louis A. Carpino | New reagents for peptide couplings |
EP1262564A3 (en) | 1993-01-07 | 2004-03-31 | Sequenom, Inc. | Dna sequencing by mass spectrometry |
US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
EP0751779B1 (en) | 1993-06-21 | 2001-12-19 | Selectide Corporation | Selectively cleavable linkers based on iminodiacetic acid ester bonds |
US5576419A (en) | 1993-06-30 | 1996-11-19 | Regents Of The University Of Minnesota | Mild solid-phase synthesis of aligned branched triple-helical peptides |
US5571902A (en) | 1993-07-29 | 1996-11-05 | Isis Pharmaceuticals, Inc. | Synthesis of oligonucleotides |
DE4343126A1 (en) | 1993-12-17 | 1995-06-22 | Hoechst Ag | Solid phase synthesis of oligoribonucleotides |
US5616698A (en) | 1994-01-10 | 1997-04-01 | University Of Toronto Innovations Foundation | Polymer-supported solution synthesis of oligosaccharides |
US5539083A (en) | 1994-02-23 | 1996-07-23 | Isis Pharmaceuticals, Inc. | Peptide nucleic acid combinatorial libraries and improved methods of synthesis |
US5679773A (en) | 1995-01-17 | 1997-10-21 | Affymax Technologies N.V | Reagants and methods for immobilized polymer synthesis and display |
US5705333A (en) | 1994-08-05 | 1998-01-06 | The Regents Of The University Of California | Peptide-based nucleic acid mimics(PENAMS) |
US5552471A (en) | 1994-08-17 | 1996-09-03 | The Perkin-Elmer Corporation | Solid support reagents for the synthesis of 3'-Nitrogen containing polynucleotides |
US6001966A (en) * | 1995-10-19 | 1999-12-14 | Proligo Llc | Method for solution phase synthesis of oligonucleotides and peptides |
US5705621A (en) | 1995-11-17 | 1998-01-06 | Isis Pharmaceuticals, Inc. | Oligomeric phosphite, phosphodiester, Phosphorothioate and phosphorodithioate compounds and intermediates for preparing same |
US5736626A (en) | 1996-01-29 | 1998-04-07 | The Perkin-Elmer Corporation | Solid support reagents for the direct synthesis of 3'-labeled polynucleotides |
CA2270132A1 (en) | 1996-11-06 | 1998-05-14 | Sequenom, Inc. | Dna diagnostics based on mass spectrometry |
JP3771660B2 (en) * | 1997-03-11 | 2006-04-26 | 大鵬薬品工業株式会社 | Branched oligonucleotide |
US7094943B2 (en) | 1998-04-27 | 2006-08-22 | Hubert Köster | Solution phase biopolymer synthesis |
-
1998
- 1998-04-27 US US09/067,337 patent/US7094943B2/en not_active Expired - Fee Related
-
1999
- 1999-04-26 AU AU36643/99A patent/AU3664399A/en not_active Abandoned
- 1999-04-26 EP EP99918819A patent/EP1073668A2/en not_active Withdrawn
- 1999-04-26 WO PCT/US1999/008939 patent/WO1999055718A2/en not_active Application Discontinuation
-
2000
- 2000-01-18 US US09/484,484 patent/US7038103B2/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1984001779A1 (en) * | 1982-10-28 | 1984-05-10 | Hubert Koester | Process for the production of oligonucleotides |
EP0642798A2 (en) * | 1993-09-08 | 1995-03-15 | La Jolla Pharmaceutical Company | Chemically-defined non-polymeric valency platform molecules and conjugates thereof |
WO1996003148A1 (en) * | 1994-07-27 | 1996-02-08 | Ono Pharmaceutical Co., Ltd. | Method and drug for treating diabetes |
WO1997014706A1 (en) * | 1995-10-19 | 1997-04-24 | Nexstar Pharmaceuticals, Inc. | Method for solution phase synthesis of oligonucleotides |
WO1999010362A1 (en) * | 1997-08-27 | 1999-03-04 | Isis Innovation Limited | Branched dendrimeric structures |
Non-Patent Citations (8)
Title |
---|
DATABASE WPI Section Ch, Week 199848 Derwent Publications Ltd., London, GB; Class B05, AN 1998-563156 XP002118884 "Branched Type Oligonucleotide" & JP 10 251292 A (TAIHO PHARM CO LTD), 22 September 1998 (1998-09-22) * |
K.SHINOZUKA ET AL.: "Novel Multifunctionalit Labelled DNA Probe Bearing an Intercalator and a Fluorophore." JOURNAL OF THE CHEMICAL SOCIETY, CHEMICAL COMMUNICATIONS., vol. 11, 1994, pages 1377-1378, XP002118883 CHEMICAL SOCIETY. LETCHWORTH., GB ISSN: 0022-4936 * |
KONIG B ET AL: "alpha-Mannosyl Clusters Scaffolded on Azamacrocycles:Synthesis and Inhibitory Properties in the Adhesion of Type 1 Fimbriated Escherichia coli to Guinea Pig Erythrocytes" TETRAHEDRON LETTERS, vol. 39, no. 16, 16 April 1998 (1998-04-16), page 2307-2310 XP004111157 ISSN: 0040-4039 * |
RITZEN A ET AL: "Phenyltrisalanine: a new, C3-symmetric, trifunctional amino acid" TETRAHEDRON: ASYMMETRY, vol. 9, no. 19, 2 October 1998 (1998-10-02), page 3491-3496 XP004141068 ISSN: 0957-4166 * |
SHCHEPINOV ET AL: "Oligonucleotide dendrimers: synthesis and use as polylabelled DNA probes" NUCLEIC ACIDS RESEARCH, vol. 25, no. 22, 1 January 1997 (1997-01-01), pages 4447-4454, XP002082740 ISSN: 0305-1048 * |
TUCHSCHERER G ET AL: "Templates in protein de novo design" JOURNAL OF BIOTECHNOLOGY, vol. 41, no. 2, 31 July 1995 (1995-07-31), page 197-210 XP004036936 ISSN: 0168-1656 * |
WORL R ET AL: "Synthesis of New Liquid Phase Carriers for Use in Large Scale Oligonucleotide Synthesis in Solution" TETRAHEDRON, vol. 55, no. 10, 5 March 1999 (1999-03-05), page 2941-2956 XP004157132 ISSN: 0040-4020 * |
WORL R ET AL: "The Use of Liquid Phase Carriers for Large Scale Oligonucleotide Synthesis in Solution via Phosphoamidite Chemistry" TETRAHEDRON, vol. 55, no. 10, 5 March 1999 (1999-03-05), page 2957-2972 XP004157133 ISSN: 0040-4020 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7038103B2 (en) | 1998-04-27 | 2006-05-02 | Hubert Koster | Solution phase biopolymer synthesis |
JP2010275254A (en) * | 2009-05-29 | 2010-12-09 | Tokyo Univ Of Agriculture & Technology | Hydrophobic group-linked nucleoside, hydrophobic group-linked nucleoside solution and method of synthesizing hydrophobic group-linked oligonucleotide |
WO2013179412A1 (en) * | 2012-05-30 | 2013-12-05 | 北海道システム・サイエンス株式会社 | Oligonucleotide synthesis method using highly dispersible liquid-phase support |
US9284344B2 (en) | 2012-05-30 | 2016-03-15 | Hokkaido System Science Co., Ltd. | Oligonucleotide synthesis method using highly dispersible liquid-phase support |
Also Published As
Publication number | Publication date |
---|---|
EP1073668A2 (en) | 2001-02-07 |
US7038103B2 (en) | 2006-05-02 |
US7094943B2 (en) | 2006-08-22 |
WO1999055718A3 (en) | 1999-12-16 |
US20020007048A1 (en) | 2002-01-17 |
US20020016451A1 (en) | 2002-02-07 |
AU3664399A (en) | 1999-11-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2627216C (en) | Polynucleotide labelling reagent | |
RU2451022C2 (en) | Cationic oligonucleotides, automated synthesis methods thereof and use thereof | |
CA2744987C (en) | Method for the synthesis of phosphorus atom modified nucleic acids | |
AU630076B2 (en) | Non-nucleotide linking reagents for nucleotide probes | |
EP0843684B1 (en) | Universal solid supports and methods for their use | |
AU706470B2 (en) | Phosphonomonoester nucleic acids, process for their preparation, and their use | |
CA2073846C (en) | Modified phosphorous intermediates for providing functional groups on the 5' end of oligonucleotides | |
USRE46171E1 (en) | Functional biopolymer modification reagents and uses thereof | |
WO2009007397A1 (en) | New polymers and their use as fluorescent labels | |
IL104461A (en) | Oligonucleotide analogs, their preparation and pharmaceutical compositions containing them | |
JP2000511562A (en) | Multifunctional binding reagents for the synthesis of branched oligomers | |
US7850949B2 (en) | Purification of synthetic oligomers | |
FR2583772A1 (en) | NOVEL SUBSTRATES, THE PREPARATION OF THESE SUBSTANCES, THE NEW INTERMEDIATES OBTAINED, THEIR APPLICATION TO THE SYNTHESIS OF OLIGONUCLEOTIDES AND THE NEW NUCLEOSIDES AND OLIGONUCLEOTIDES RELATING TO THE SUBSTANCES THUS OBTAINED | |
US5623068A (en) | Synthesis of DNA using substituted phenylacetyl-protected nucleotides | |
US7038103B2 (en) | Solution phase biopolymer synthesis | |
FI111265B (en) | Process for the preparation of modified oligodeoxyribonucleotides useful as pharmaceuticals and intermediates thereof | |
US20030129593A1 (en) | Process for producing multiple oligonucleotides on a solid support | |
US8394948B2 (en) | Reagents utilizing a serinol scaffold for labeling synthetic oligonucleotides | |
US20130053258A1 (en) | Combinatorial library, a method for preparation of that combinatorial library, a method for sequence identification, a method for sequencing the elements of combinatorial libraries of oligonucleotides and/or oligonucleotide analogues, the use of a linker to generate combinatorial libraries and a sequence identification set | |
MXPA01004672A (en) | Polynucleotide crosslinking agents. | |
JP2002503265A (en) | Novel monomer constructs for labeling peptide nucleic acids | |
US20040101839A1 (en) | Novel functional peptide nucleic acid monomer and process for producing the same | |
JP2005517709A (en) | Bifunctional metallocene, process for its production and use in the labeling of biological molecules | |
WO2023022055A1 (en) | Modified polynucleotide | |
WO2011097092A2 (en) | Solid-supported ether disulfides |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1999918819 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1999918819 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1999918819 Country of ref document: EP |