Novel 3'-modified oligonucleotide derivatives

• Main Authors: EUGEN UHLMANN, CAROLIN CAROLUS, ANUSCHIRWAN PEYMAN
• Format: Patent
• Language: English
• Published: 21.12.1995
• Edition: 6
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS BASED THEREON; COMPOSITIONS OR TEST PAPERS THEREFOR; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; DERIVATIVES THEREOF; ENZYMOLOGY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONSONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MUTATION OR GENETIC ENGINEERING; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; ORGANIC MACROMOLECULAR COMPOUNDS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROCESSES OF PREPARING SUCH COMPOSITIONS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; STEROIDS; SUGARS; THEIR PREPARATION OR CHEMICAL WORKING-UP; VINEGAR; WINE

3'-Derivatised oligonucleotide analogues of formula (I) and (II) and their salts are new: R -(A )n'-(B )m'-(A )n-(B )m-B (I); R -(A )n'-(B )m'-(A )n-A (II); A and A = gps. of formula (i); B and B = gps. of formula (ii); B = a gp. of formula (iii); and A = a gp. of formula (iv); a and b = 0 to 20; R = H, 1-18C alkyl, 2-18C alkenyl, 3-18C alkynyl, 2-19C alkanoyl, 3-20C alkenoyl, 4-20C alkynoyl, 6-20C aryl, (6-14C)aryl(1-8C)alkyl or P(W)ZZ'; R = H, OH, 1-18C alkoxy, halogen, azido or NH2; D = OH or OPO3<2->; B = a natural or unnatural nucleotide base; n = 1-100; n' = 0-50; m = 0-5; m' = 0-5 in (I) or 1-5 in (II); A = O, S or CH2; W = O, S or Se; V = O or S; T = O, S or NH; Y = O, S, NH or CH2; X = OH or SH; U = OH, SH, BH3 (sic), SeH, 1-18C alkoxy, 1-18C alkyl, 6-20C aryl, (6-14C)aryl(1-8C)alkyl, NHR , NR R or (OCH2CH2)pO(CH2)qCH2R ; R = 1-18C alkyl, 6-20C aryl, (6-14C)aryl(1-8C)alkyl or (CH2)c(NH(CH2)c)dNR R ; c = 2-6; d = 0-6; R = H, 1-6C alkyl or (1-4C)alkoxy(1-6C)alkyl; R = 1-18C alkyl, 6-20C aryl or (6-14C)aryl(1-8C)alkyl; or NR R = a 5- or 6-membered ring opt. contg. another N, O or S atom; p = 1-100; q = 0-22; R = H or a functional gp. such as OH, NH2, NHR , COOH, CONH2, COOR or halogen; R = 1-6C alkyl, R = 1-4C alkyl; Z and Z' = OH, SH, SeH, 1-22C alkoxy, O(CH2)bNHR 'R ', 1-18C alkyl, 6-20C aryl, (6-14)aryl(1-8C)alkyl (where aryl includes heteroaryl and is opt. substd. by 1-3 of COOH, NH2, NO2, 1-4C alkylamino, 1-6C alkoxy, OH, halogen and CN), 1-18C alkylthio, NHR , NR R , a 3'- or 5'-linked nucleoside or oligonucleotide, or a gp. which enhances intracellular uptake, serves as a DNA probe label or binds to, crosslinks with or cleaves a target nucleic acid after hybridisation; R 'R ' = as R , R ; or NR 'R = a 3- to 6-membered ring.