CA2144475A1 - Polyamide-oligonucleotide derivatives, their preparation and use - Google Patents
Polyamide-oligonucleotide derivatives, their preparation and useInfo
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- CA2144475A1 CA2144475A1 CA002144475A CA2144475A CA2144475A1 CA 2144475 A1 CA2144475 A1 CA 2144475A1 CA 002144475 A CA002144475 A CA 002144475A CA 2144475 A CA2144475 A CA 2144475A CA 2144475 A1 CA2144475 A1 CA 2144475A1
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- 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
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- 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
- A61K47/51—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 the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
-
- 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
- A61K47/51—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 the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/595—Polyamides, e.g. nylon
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- 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
- A61K47/51—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 the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
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- 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)
Abstract
Polyamide-oligonucleotide derivatives of the formula F[(DNA-Li)q(PNA-Li)r(DNA-Li)s(PNA)t]yF' wherein q, r, s, t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s and t ? 2; x is 1 to 20; DNA is a nucleic acid such as DNA or RNA or a known derivative thereof; Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O or S; PNA is a polyamide structure which contains at least one nucleotide base which is different from thymine; and F and F' are end groups and/or are linked together by a covalent bond, and the physiologically tolerated salts thereof, a process for their preparation and their use as pharmaceutical, as gene probe and as primer, are described.
Claims (15)
1. A polyamide-oligonucleotide derivative of the for-mula I
Ft(DNA-Li)q(PNA-Li)r(DNA-Li)s(PNA)t]xF' (I) wherein q, r, s, t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s and t > 2;
x is 1 to 20, 1;
DNA is a nucleic acid such as DNA or RNA or a known derivative thereof;
Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O or S;
PNA is a polyamide structure which contains at least one nucleotide base which is different from thymine; and F and F' are end groups and/or are linked together by a covalent bond, and the physiologically tolerated salts thereof.
Ft(DNA-Li)q(PNA-Li)r(DNA-Li)s(PNA)t]xF' (I) wherein q, r, s, t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s and t > 2;
x is 1 to 20, 1;
DNA is a nucleic acid such as DNA or RNA or a known derivative thereof;
Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O or S;
PNA is a polyamide structure which contains at least one nucleotide base which is different from thymine; and F and F' are end groups and/or are linked together by a covalent bond, and the physiologically tolerated salts thereof.
2. A polyamide-oligonucleotide derivative as claimed in claim 1, wherein x is 1 to 5.
3. A polyamide-oligonucleotide derivative as claimed in claim 1, wherein x is 1.
4. A polyamide-oligonucleotide derivative as claimed in claim 1, wherein x is 1 and q = r = 1 and s = t = zero or r = s = 1 and q = t = zero or q = r = s = 1 and t = zero or r = s = t = 1 and q = zero.
5. A polyamide-oligonucleotide derivative of the for-mulae Ia and Ib as claimed in claims 1 to 4, (1a) (1b) wherein x is 1 to 20, where when x > 1 r = s = 1 and, at the same time, q = t = zero and o = n = zero to 5;
q, r, s, t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s and t ? 2;
R2 is hydrogen, hydroxyl, C1-C18-alkoxy, halogen, azido or amino;
B is, independently of one another, a base custo-mary in nucleotide chemistry, for example natural bases such as adenine, cytosine, thymine, guanine, uracil, inosine or unnatural bases such as, for example, purine, 2,6-di-aminopurine, 7-deazaadenine, 7-deazaguanine, N4,N4-ethanocytosine, N6,N6-ethano-2,6-diamino-purine, pseudoisocytosine, 5-methylcytosine, 5-fluorouracil, 5-(C3-C6)-alkynyluracil, 5-(C3-C6)-alkynylcytosine or the prodrug forms thereof, and the "curved bracket" indicates that R2 and the adjacent substituent can be in the 2' posi-tion and 3' position or else conversely in the 3' position and 2' position;
Nu is a radical of the formulae IIa or IIb (11a) (11b) in which R2 and B are as defined above;
U is hydroxyl, mercapto, C1-C18-alkyl, C1-C18-alkoxy, C6-C20-aryl, C6-C14-aryl-C1-C8-alkyl, NHR3 or NR3R4, and R3 is C1-C18-alkyl or C1-C4-alkoxy-C1-C4-alkyl, and R4 is C1-C18-alkyl or R3 and R4 is, together with the nitrogen atom carry-ing them, a 5-6-membered heterocyclic ring which can additionally contain another hetero-atom from the series consisting of O, S, N;
V is oxy, thio or imino;
W is oxo or thioxo;
Y is oxy, thio, methylene or imino;
m is zero to 20;
o is zero to 20;
D is a radical of the formula III
(III) in which B is as defined above;
D' is a radical of the formula IV
(IV) in which B is as defined above;
n is zero to 20;
p is zero to 20;
Li1, Li2, Li3 and Li4 are each, independently of one another, a structure of the formula V
[(V')-(G)-(G')]? (V) where, independently of one another, ? is 1 to 5, V' is oxygen, NH, a bond or a radical of the formula VI
(VI) in which U, V, W and Y are as defined above;
G can be C1-C12-alkanediyl, where alkanediyl can optionally be substituted by halogen, amino, hydroxyl, C1-C18-alkyl, C1-C18-alkoxy, C6-C14-aryl, or C6-C14-aryl-C1-C18-alkyl; C6-C14-aryl-di-C1-C12-alkanediyl, or a group of the formula (CH2CH2O).delta.CH2CH2 in which .delta. can be 1 to 11; or a bond; and G' is oxy, thio, imino, -C(O)-, -C(O)NH-, a bond or a radical of the formula VI in which U, V, W and Y are as defined above; and F and F' are linked by a bond and/or F is R0 - (A)k - V - and F' in formula Ia is _ (Q)1 - R1 and in formula Ib is V1 - (A)1 - R1, where R0 is hydrogen, C1-C18-alkanoyl, C1-C18-alkoxy-carbonyl, C3-C8-cycloalkanoyl, C7-C15-aroyl, C3-C13-heteroaroyl or a group which favors intracellular uptake of the oligomer or serves as labeling of a DNA probe or, in the hybridization of the oligomer onto the target nucleic acid, attacks the latter with binding, crosslinking or cleavage; or if k is zero, R0 is hydrogen or together with V is a radical of the formula VII
(VII) in which Z and Z' are, independently of one another, hydroxyl, mercapto, C1-C22-alkoxy, C1-C18-alkyl, C6-C20-aryl, C6-C14-aryl-C1-C18-alkyl, C1-C22-alkylthio, NHR3, NR3R4, or a group which favors intracellular uptake of the oligomer or serves as labeling of a DNA probe or, in the hybridi-zation of the oligomer onto the target nucleic acid, attacks the latter with binding, cross-linking or cleavage, and in which R3, R4, V and W are as defined above;
R1 is hydrogen or Q°
where R1 is always only hydrogen when at the same time 1 is zero and in formula Ia t is zero and s is 1 and Li1 is a struc-ture of the formula V with V' = bond, G = bond, ? = 1 and G' = oxy, thio, imino or a radical of the formula VI with U = Z
or in formula Ib q is 1 or q = r = zero and in F' = V1 - (A)1 _ R1 with V1 = V, A and Q are, independently of one another, the residue of a natural or unnatural amino acid, preferably from the series consisting of glycine, leucine, histidine, phenylalanine, cysteine, lysine, arginine, aspartic acid, glutamic acid, proline, tetrahydroisoquinoline-3-carboxylic acid, octahydroindole-2-carboxylic acid, N-(2-aminoethyl)glycine;
Q° is hydroxyl, OR', NH2, NHR" with R' = C1-C18-alkyl and R = C1-C18-alkyl, C1-C18-aminoalkyl, C1-C18-hydroxyalkyl;
V is as defined above;
V1 is a bond or V, where in F' only in for-mula Ib with q = zero and r = 1 v1 is always a bond;
k is zero to 10;
l is zero to 10;
with the proviso that a) if in the compound of the formula Ia t is zero and s is 1, and Li1 is (V') - (G) - (G') with V' = a compound of the formula VI, G = C2-C12-alkylene and G' = CO, in F' = - (Q)1 - R1 1 is zero to 10 and R1 is Q°;
b) if in the compound of the formula Ia s = t = zero, Li2 is a bond;
c) if in the compound of the formula Ib t is zero and s is 1, Li3 is a bond;
d) if in the compound of the formula Ib s = t = zero, Li4 is a bond;
where each nucleotide can be in its D or L configu-ration, and the base can be in the .alpha. or .beta. position.
q, r, s, t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s and t ? 2;
R2 is hydrogen, hydroxyl, C1-C18-alkoxy, halogen, azido or amino;
B is, independently of one another, a base custo-mary in nucleotide chemistry, for example natural bases such as adenine, cytosine, thymine, guanine, uracil, inosine or unnatural bases such as, for example, purine, 2,6-di-aminopurine, 7-deazaadenine, 7-deazaguanine, N4,N4-ethanocytosine, N6,N6-ethano-2,6-diamino-purine, pseudoisocytosine, 5-methylcytosine, 5-fluorouracil, 5-(C3-C6)-alkynyluracil, 5-(C3-C6)-alkynylcytosine or the prodrug forms thereof, and the "curved bracket" indicates that R2 and the adjacent substituent can be in the 2' posi-tion and 3' position or else conversely in the 3' position and 2' position;
Nu is a radical of the formulae IIa or IIb (11a) (11b) in which R2 and B are as defined above;
U is hydroxyl, mercapto, C1-C18-alkyl, C1-C18-alkoxy, C6-C20-aryl, C6-C14-aryl-C1-C8-alkyl, NHR3 or NR3R4, and R3 is C1-C18-alkyl or C1-C4-alkoxy-C1-C4-alkyl, and R4 is C1-C18-alkyl or R3 and R4 is, together with the nitrogen atom carry-ing them, a 5-6-membered heterocyclic ring which can additionally contain another hetero-atom from the series consisting of O, S, N;
V is oxy, thio or imino;
W is oxo or thioxo;
Y is oxy, thio, methylene or imino;
m is zero to 20;
o is zero to 20;
D is a radical of the formula III
(III) in which B is as defined above;
D' is a radical of the formula IV
(IV) in which B is as defined above;
n is zero to 20;
p is zero to 20;
Li1, Li2, Li3 and Li4 are each, independently of one another, a structure of the formula V
[(V')-(G)-(G')]? (V) where, independently of one another, ? is 1 to 5, V' is oxygen, NH, a bond or a radical of the formula VI
(VI) in which U, V, W and Y are as defined above;
G can be C1-C12-alkanediyl, where alkanediyl can optionally be substituted by halogen, amino, hydroxyl, C1-C18-alkyl, C1-C18-alkoxy, C6-C14-aryl, or C6-C14-aryl-C1-C18-alkyl; C6-C14-aryl-di-C1-C12-alkanediyl, or a group of the formula (CH2CH2O).delta.CH2CH2 in which .delta. can be 1 to 11; or a bond; and G' is oxy, thio, imino, -C(O)-, -C(O)NH-, a bond or a radical of the formula VI in which U, V, W and Y are as defined above; and F and F' are linked by a bond and/or F is R0 - (A)k - V - and F' in formula Ia is _ (Q)1 - R1 and in formula Ib is V1 - (A)1 - R1, where R0 is hydrogen, C1-C18-alkanoyl, C1-C18-alkoxy-carbonyl, C3-C8-cycloalkanoyl, C7-C15-aroyl, C3-C13-heteroaroyl or a group which favors intracellular uptake of the oligomer or serves as labeling of a DNA probe or, in the hybridization of the oligomer onto the target nucleic acid, attacks the latter with binding, crosslinking or cleavage; or if k is zero, R0 is hydrogen or together with V is a radical of the formula VII
(VII) in which Z and Z' are, independently of one another, hydroxyl, mercapto, C1-C22-alkoxy, C1-C18-alkyl, C6-C20-aryl, C6-C14-aryl-C1-C18-alkyl, C1-C22-alkylthio, NHR3, NR3R4, or a group which favors intracellular uptake of the oligomer or serves as labeling of a DNA probe or, in the hybridi-zation of the oligomer onto the target nucleic acid, attacks the latter with binding, cross-linking or cleavage, and in which R3, R4, V and W are as defined above;
R1 is hydrogen or Q°
where R1 is always only hydrogen when at the same time 1 is zero and in formula Ia t is zero and s is 1 and Li1 is a struc-ture of the formula V with V' = bond, G = bond, ? = 1 and G' = oxy, thio, imino or a radical of the formula VI with U = Z
or in formula Ib q is 1 or q = r = zero and in F' = V1 - (A)1 _ R1 with V1 = V, A and Q are, independently of one another, the residue of a natural or unnatural amino acid, preferably from the series consisting of glycine, leucine, histidine, phenylalanine, cysteine, lysine, arginine, aspartic acid, glutamic acid, proline, tetrahydroisoquinoline-3-carboxylic acid, octahydroindole-2-carboxylic acid, N-(2-aminoethyl)glycine;
Q° is hydroxyl, OR', NH2, NHR" with R' = C1-C18-alkyl and R = C1-C18-alkyl, C1-C18-aminoalkyl, C1-C18-hydroxyalkyl;
V is as defined above;
V1 is a bond or V, where in F' only in for-mula Ib with q = zero and r = 1 v1 is always a bond;
k is zero to 10;
l is zero to 10;
with the proviso that a) if in the compound of the formula Ia t is zero and s is 1, and Li1 is (V') - (G) - (G') with V' = a compound of the formula VI, G = C2-C12-alkylene and G' = CO, in F' = - (Q)1 - R1 1 is zero to 10 and R1 is Q°;
b) if in the compound of the formula Ia s = t = zero, Li2 is a bond;
c) if in the compound of the formula Ib t is zero and s is 1, Li3 is a bond;
d) if in the compound of the formula Ib s = t = zero, Li4 is a bond;
where each nucleotide can be in its D or L configu-ration, and the base can be in the .alpha. or .beta. position.
6. A polyamide-oligonucleotide derivative of the formulae Ia and Ib as claimed in claim 5, wherein the base is in the .beta. position.
7. A process for the preparation of polyamide-oligonucleotide derivatives as claimed in claims 1 to 6, which comprises successive condensation of a PNA unit or DNA unit with, in each case, one nucleotide base onto an appropriately derivatized support or onto a growing oligomer chain.
8. A polyamide-oligonucleotide derivative as claimed in claims 1 to 6 for use as medicine.
9. A polyamide-oligonucleotide derivative as claimed in claims 1 to 6 for use as medicine for the treatment of diseases caused by viruses or of diseases influenced by integrins or cell-cell adhesion receptors, for the treatment of cancer or for pre-venting restenosis.
10. A pharmaceutical containing a polyamide-oligonucleo-tide derivative as claimed in claims 1 to 6.
11. A polyamide-oligonucleotide derivative as claimed in claims 1 to 6 for use as gene probe.
12. A polyamide-oligonucleotide derivative as claimed in claims 1 to 6, wherein a nucleoside unit having a 3'-hydroxyl group is located on at least one end for use as primer.
13. A gene probe assay for the determination of an oligo- or polynucleotide target (RNA or DNA), wherein a gene probe as claimed in claim 11 is used in a homogeneous or heterogeneous assay.
14. A gene probe assay for the determination of an oligo- or polynucleotide target (RNA or DNA), wherein a primer as claimed in claim 12 is used.
15. A gene probe assay as claimed in claims 13 and 14, wherein the target is determined by hybridization after target amplification.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4408528A DE4408528A1 (en) | 1994-03-14 | 1994-03-14 | Peptide oligonucleotide derivatives, their preparation and use |
| DEP4408528.1 | 1994-03-14 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2144475A1 true CA2144475A1 (en) | 1995-09-15 |
| CA2144475C CA2144475C (en) | 2010-06-08 |
Family
ID=6512694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2144475A Expired - Fee Related CA2144475C (en) | 1994-03-14 | 1995-03-13 | Polyamide-oligonucleotide derivatives, their preparation and use |
Country Status (14)
| Country | Link |
|---|---|
| EP (2) | EP0672677B1 (en) |
| JP (1) | JP4620810B2 (en) |
| KR (1) | KR100416864B1 (en) |
| CN (1) | CN100379756C (en) |
| AT (2) | ATE220070T1 (en) |
| AU (1) | AU698210B2 (en) |
| CA (1) | CA2144475C (en) |
| DE (3) | DE4408528A1 (en) |
| DK (2) | DK1113021T3 (en) |
| ES (2) | ES2179080T3 (en) |
| FI (2) | FI117135B (en) |
| HK (2) | HK1038568A1 (en) |
| NO (1) | NO314664B1 (en) |
| PT (2) | PT1113021E (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5874553A (en) * | 1995-03-13 | 1999-02-23 | Hoechst Aktiengesellschaft | Phosphonomonoester nucleic acids, process for their preparation, and their use |
| US6013639A (en) * | 1995-01-31 | 2000-01-11 | Hoechst Aktiengesellschaft | G cap-stabilized oligonucleotides |
| US6191165B1 (en) | 1996-05-31 | 2001-02-20 | Allelix Neuroscience Inc. | Pharmaceutical for treatment of neurological and neuropsychiatric disorders |
| US6905820B2 (en) | 2000-04-18 | 2005-06-14 | Aventis Pharma Deutschland Gmbh | Polyamide nucleic acid derivatives, and agents and processes for preparing them |
| US7759126B2 (en) | 2003-10-28 | 2010-07-20 | Elitech Holding B.V. | Real-time linear detection probes: sensitive 5′-minor groove binder-containing probes for amplification (or PCR) analysis |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6710164B1 (en) | 1993-11-22 | 2004-03-23 | Peter E. Nielsen | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| DE4438918A1 (en) * | 1994-11-04 | 1996-05-09 | Hoechst Ag | Modified oligonucleotides, their preparation and their use |
| US6150510A (en) | 1995-11-06 | 2000-11-21 | Aventis Pharma Deutschland Gmbh | Modified oligonucleotides, their preparation and their use |
| DE19532553A1 (en) * | 1995-09-04 | 1997-03-06 | Hoechst Ag | Process for the preparation of substituted N-ethyl-glycine derivatives |
| GB2324534B (en) * | 1996-01-06 | 2000-05-10 | Danbiosyst Uk | Composition for delivery of nucleic acid to a cell |
| ES2221942T3 (en) * | 1996-05-24 | 2005-01-16 | Aventis Pharma Deutschland Gmbh | REAGENT AND METHOD TO INHIBIT THE EXPRESSION OF N-RAS. |
| SK285854B6 (en) * | 1996-05-31 | 2007-09-06 | Allelix Neuroscience Inc. | Substituted amine and pharmaceutical composition, their use and method for preparing the amine |
| DE69734783T2 (en) * | 1996-07-24 | 2006-08-17 | Buchardt, Dorte | PEPTID NUCLEIC ACIDS WITH INCREASED BINDING SAFFINITY, SEQUENCE SPECIFICITY AND SOLUBILITY |
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| EP0972779A3 (en) * | 1987-10-28 | 2004-10-20 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates |
| WO1993024511A1 (en) * | 1992-05-29 | 1993-12-09 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates |
| US5138045A (en) * | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| DK51092D0 (en) * | 1991-05-24 | 1992-04-15 | Ole Buchardt | OLIGONUCLEOTIDE ANALOGUE DESCRIBED BY PEN, MONOMERIC SYNTHONES AND PROCEDURES FOR PREPARING THEREOF, AND APPLICATIONS THEREOF |
| US5646261A (en) * | 1992-01-22 | 1997-07-08 | Hoechst Aktiengesellschaft | 3'-derivatized oligonucleotide analogs with non-nucleotidic groupings, their preparation and use |
| IL104461A (en) * | 1992-01-22 | 2001-05-20 | Hoechst Ag | Oligonucleotide analogs, their preparation and pharmaceutical compositions containing them |
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- 1994-03-14 DE DE4408528A patent/DE4408528A1/en not_active Withdrawn
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- 1995-03-08 ES ES95103332T patent/ES2179080T3/en not_active Expired - Lifetime
- 1995-03-08 EP EP95103332A patent/EP0672677B1/en not_active Expired - Lifetime
- 1995-03-08 EP EP01104012A patent/EP1113021B1/en not_active Expired - Lifetime
- 1995-03-08 DK DK01104012T patent/DK1113021T3/en active
- 1995-03-08 DE DE59511061T patent/DE59511061D1/en not_active Expired - Lifetime
- 1995-03-08 DE DE59510252T patent/DE59510252D1/en not_active Expired - Lifetime
- 1995-03-08 PT PT01104012T patent/PT1113021E/en unknown
- 1995-03-08 ES ES01104012T patent/ES2269239T3/en not_active Expired - Lifetime
- 1995-03-08 AT AT95103332T patent/ATE220070T1/en active
- 1995-03-08 AT AT01104012T patent/ATE335760T1/en active
- 1995-03-08 DK DK95103332T patent/DK0672677T3/en active
- 1995-03-08 PT PT95103332T patent/PT672677E/en unknown
- 1995-03-10 AU AU14798/95A patent/AU698210B2/en not_active Ceased
- 1995-03-10 FI FI951132A patent/FI117135B/en not_active IP Right Cessation
- 1995-03-13 CA CA2144475A patent/CA2144475C/en not_active Expired - Fee Related
- 1995-03-13 CN CNB951029460A patent/CN100379756C/en not_active Expired - Lifetime
- 1995-03-13 NO NO19950955A patent/NO314664B1/en not_active IP Right Cessation
- 1995-03-14 JP JP05464495A patent/JP4620810B2/en not_active Expired - Fee Related
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1998
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- 1998-12-11 HK HK98113225A patent/HK1012003A1/en not_active IP Right Cessation
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2005
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6013639A (en) * | 1995-01-31 | 2000-01-11 | Hoechst Aktiengesellschaft | G cap-stabilized oligonucleotides |
| US6121434A (en) * | 1995-01-31 | 2000-09-19 | Aventis Pharma Deutschland Gmbh | G cap-stabilized oligonucleotides |
| US7229974B2 (en) | 1995-01-31 | 2007-06-12 | Sanofi-Aventis Deutschland Gmbh | G cap-stabilized oligonucleotides |
| US5874553A (en) * | 1995-03-13 | 1999-02-23 | Hoechst Aktiengesellschaft | Phosphonomonoester nucleic acids, process for their preparation, and their use |
| US6127346A (en) * | 1995-03-13 | 2000-10-03 | Hoechst Aktiengesellschaft | Phosphonomonoester nucleic acids process for their preparation and their use |
| US6191165B1 (en) | 1996-05-31 | 2001-02-20 | Allelix Neuroscience Inc. | Pharmaceutical for treatment of neurological and neuropsychiatric disorders |
| US7019024B2 (en) | 1996-05-31 | 2006-03-28 | Allelix Neuroscience Inc. | Pharmaceutical for treatment of neurological and neuropsychiatric disorders |
| US6905820B2 (en) | 2000-04-18 | 2005-06-14 | Aventis Pharma Deutschland Gmbh | Polyamide nucleic acid derivatives, and agents and processes for preparing them |
| US7550582B2 (en) | 2000-04-18 | 2009-06-23 | Sanofi-Aventis Deutschland Gmbh | Polyamide nucleic acid derivatives and agents, and processes for preparing them |
| US7897346B2 (en) | 2000-04-18 | 2011-03-01 | Sanofi-Aventis Deutschland Gmbh | Polyamide nucleic acid derivatives and agents, and processes for preparing them |
| US8268560B2 (en) | 2000-04-18 | 2012-09-18 | Sanofi-Aventis Deutschland Gmbh | Polymide nucleic acid derivatives, and agents and processes for preparing them |
| US7759126B2 (en) | 2003-10-28 | 2010-07-20 | Elitech Holding B.V. | Real-time linear detection probes: sensitive 5′-minor groove binder-containing probes for amplification (or PCR) analysis |
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