Methods of using oligomers containing modified pyrimidines

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

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435325, 435375, 514 44, 536 245, C12Q 168, C12N 506, C12N 510, C07H 2100

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058306536

ABSTRACT:
Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. compositions of the invention can be used as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

REFERENCES:
patent: 4415732 (1983-11-01), Caruthers et al.
patent: 4458066 (1984-07-01), Caruthers et al.
patent: 4725677 (1988-02-01), Koster
patent: 4959463 (1990-09-01), Froehler et al.
patent: 5013830 (1991-05-01), Ohtsuka et al.
patent: 5034506 (1991-07-01), Summerton et al.
patent: 5204455 (1993-04-01), Froehler et al.
patent: 5256775 (1993-10-01), Froehler
patent: 5264423 (1993-11-01), Cohen et al.
patent: 5264564 (1993-11-01), Matteucci
patent: 5272057 (1993-12-01), Smulson
patent: 5399676 (1995-03-01), Froehler
patent: 5440040 (1995-08-01), Gronowitz
patent: 5466786 (1995-11-01), Buhr et al.
patent: 5495009 (1996-02-01), Matteucci et al.
patent: 5596086 (1997-01-01), Matteucci et al.
Graessmann et al. Inhibition of SV40 gene expression by microinjection of small antisnese RNA and DNA molecules. Nucleic acid Res. 19(1): 53-59,1990.
Booras et al. Evidence for positive and negative regulation in the promoter of the chicken d1-crystallin gene. Developmental Biol. 127(1):209-219.
Alderfer et al., "Comparative Studies on Homopolymers of Adenylic Acid Possessing Different C-2' Substituents of the Furanose. Poly(deoxyriboadenylic acid), Poly(riboadenylic acid), Poly(2'-0-methyladenylic acid), and Poly(2'-0-ethyladenylic acid)," Biochem 13(8):1615-1622 (1974).
Kielanowska et al., "Preparation and Properties of Poly'-O-Ethylcytidylic Acid," Nuc Acids Res 3(3):817-824 (Mar. 1976).
Ransford et al., "2-O-Ethyl Pyrimidine Nucleosides (1)," J Carbohydrates Nucls Nuclt 1(3):275-278 (1974).
Guathier-Rouviere et al., "Casein kinase II induces c-fos expression via the serum response element pathway and p67srf phosphorylation in living fibroblasts," Embo J 10(10):2921-2930 (1991).
Hollon et al., "Variation in Enzymatic Transient Gene Expression Assays," Anal Biochem 182:411-418 (1989).
Lamb et al., "Demonstration in Living Cells of an Intragenic Negative Regulatory Element within the Rodent c-fos Gene," Cell 61:485-496 (1990).
Riabowol et al., "Microinjection of fos-Specific Antibodies Blocks DNA Synthesis in Fibroblast Cells.," Mol Cell Biol 8(4)1670-1676 (Apr. 1988).
Hobbs et al., "Palladium-Catlyzed Synthesis of Alkynylamino Nucleosides. A Universal Linker for Nucleic Acids," J Org Chem 54:3420-3422 (1989).
Kumar et al., "Synthesis and Antiviral Activity of Novel-5(1-Azido-2-haloethyl) and 5-(1-Azido-, amino-, or methoxyethyl) Analogs of 2'-Deoxyuridine," J Med Chem 36:2470-2474 (1993).
Leusink et al., "Studies in Group IV Organometallic Chemistry XXIV. Structure of Products Obtained in the Hydrostannation of Ethynes," J Organometal Chem 9:285-294 (1967).
Loke et al., "Characterization of oligonucleotide transport into living cells," Proc Natl Acad Sci 86:3474-3478 (1989).
Robins et al., "Nucleic Acid Related Compounds. 31. Smooth and Efficient Palladium-Copper Catalyzed Coupling of Terminal Alkynes with 5-Iodouracil Nucleosides," Tet Lett 22:421-424 (1981).
Robins et al., "Nucleic Acid Related Compounds. 39. Efficient Conversion of 5-lodo to 5-Alkynyl and Derived 5-Substituted Uracil Bases and Nucleosides," J Org Chem 48:1854-1862 (1983).
Robins et al., "Solvent, Not Palladium Oxidation State, is the Primary Determinant for Successful Coupling of Terminal Alkynes with lodo-Nucleosides," Tet Lett 31(26):3731-3734 (1990).
Vincent et al., "Alcynyl-5 Desoxy-2' Uridines Par Couplages D'Organozinciques Acetyleniques Avec L'iodo-5 0-3', 5'-Bis(Trimethylsilyl) Desoxyuridine, Catalyses Par Des Complexes Organopalladies et de Nickel," Tet Lett 22:945-947 (1981).
Augustyns et al., "Incorporation of hexose nucleoside analogues into oligonucleotides: synthesis, base-pairing properties and enzymatic stability," Nuc Acids Res 20:4711-4716 (1992).
Chiang et al., "Antisense Oligonucleotides Inhibit Intercellular Adhesion Molecule 1 Expression by Two Distinct Mechanisms," J Biol Chem 266:18162-18171 (1991).
Clivio et al., "Synthesis of Dinucleoside Phosphates Containing Sulfur Substutited Nucleobase: 4-Thiouracil, 4-Thiothymine and 6-Mercaptopurine," Tet Lett 33:69-72 (1992).
Connolly et al., "Synthesis and properties of oligonucleotides containing 4-thiothymidine, 5-methyl-2-pyrimidinone-1-b-D(2'-deoxyriboside) and 2-thiothymidine," Nuc Acids Res 17:4957-4974 (1989).
Cooney et al., "Site-Specific Oligonucleotide Binding Represses Transcription of the Human c-myc Gene In Vitro," Science 241:456-459 (1988).
De Clercq et al., "Nucleic Acid Related Compounds. 40. Synthesis and Biological Acitivities of 5-Alkynyluracil Nucleosides," J Med Chem 26:661-666 (1983).
Egholm et al., "Peptide Nucleic Acids (PNA). Oligonucleotide Analogues with an Achiral Peptide Backbone," J Am Chem Soc 114:1895-1897 (1992).
Fedorovo et al., "Complementary addressed modification of double-stranded DNA within a ternary complex," Febs 228:273-276 (1988).
Felgner et al., "Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure," Proc Natl Acad Sci 84:7413-7417 (1987).
Froehler et al., "Oligodeoxynucleotides Containg C-5 Propyne Anaologs of 2'-Deoxyuridine and 2'-Deoxycytidine," Tet Lett 33:5307-5310 (1992).
Froehler et al., "Triple-Helix Formation and Cooperative Binding by Oligodeoxynucleotides with a 3'-3' Internucleotide Junction," Biochem 31:1603-1609 (1992).
Froehler et al., "Triple-Helix Formation by Oligodeoxynucleotides Containing the Carbocyclic Analogs of Thymidine and 5-Methyl-2-deoxycytidine," J Am Chem Soc 114:8320-8322 (1992).
Goodchild et al., "Structural Requirements of Olefinic 5-Substituted Deoxyuridines for Antiherpes Activity," J Med Chem 26:1252-1257 (1983).
Iverson et al., "Nonenzymatic Sequence-Specific Cleavage of Single-Stranded DNA to Nucleotide Resolution. DNA Methyl Thioether Probes," J Am Chem Soc 109:1241-1243 (1987).
Knorre et al., "Reactive oligonucleotide derivatives and sequence-specific modification of nucleic acids," Biochimie 67:785-789 (1985).
Lee et al., "Interaction of Psoralen-Derivatized Oligodexoyribonucleoside Methylphosphonates with Single-Stranded DNA," Biochem 27:3197-3203 (1988).
Lee et al., "Poly(pyrimidine) .cndot. poly(purine) synthetic DNAs containing ???," Nuc Acids Res 12:6603-6614 (1984).
Maher et al., "Inhibition of DNA Binding Proteins by Oligonucleotide-Directed Triple Helix Formation," Science 245:725-730 (1989).
Matteucci et al., "Synthesis and Crosslinking Properties of a 28:2469-2472 (1987).
Meyer et al., "Efficient, Specific Cross-Linking and Cleavage of DNA by Stable, Synthetic Complementary Oligodeoxynucleotides," J Am Chem Soc 111:8517-8519 (1989).
Murakami et al, "Highly sensitive detection of DNA using enzyme-linked DNA-probe. 1. Colorimetric and fluorometric detection," Nuc Acids Res 17(14)5587-5595 (1989).
Nielson et al., "Sequence-Selective Recognition of DNA by Strand Displacement with a Thymine-Substituted Polyamide," Science 254:1497-1500 (1991).
Otvos et al., "Substrate specificity of DNA polymerases. I. Enzyme-catlysed incorporation of 5-(1-alkenyl)-2'-deoxyuridines into DNA," Nuc Acids Res 15:1763-1777 (1987).
Otvos et al., "Substrate specificity of DNA polymerases. II. 5-(1-Alkynyl)-dUTPs as substrates of the Klenow DN

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