Exonuclease resistant terminally substituted oligonucleotides

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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536 2532, C07H 2100

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active

052450228

ABSTRACT:
Compounds, compositions and methods for inhibiting gene expression are disclosed. The compounds comprise oligonucleotide sequences of from about 9 to about 200 bases having a diol at either or both termini. Preferred diols are polyalkyleneglycols, preferably polyethyleneglycols. Pharmaceutical compositions comprising the compounds and a physiologically acceptable carrier and methods of inhibiting gene expression in mammals comprising administering such compounds are also provided. Methods for inhibiting nuclease cleavage of compounds are also provided.

REFERENCES:
Stirchak et al., "Uncharged Stereoregular Nucleic Acid Analogues. I. Synthesis of a Cytosine-Containing Oligomer with Carbamate Internucleoside Linkages", J. Org. Chem., 52, 4202-4206 (1987).
Mungall et al., "Carbamate Analogues of Oligonucleotides", J. Org. Chem., vol. 42, No. 4, 1977, pp. 703-706.
Coull et al., "Synthesis and Characterization of a Carbamate-Linked Oligonucleoside", Tetrahedron Letters, vol. 28, No. 7, pp. 745-748, 1987.
Schneider et al., "Building Blocks for Oligonucleotide Analogs with Dimethylene-Sulfide, --Sulfoxide, and --Sulfone Groups Replacing Phosphodiester Linkages", Tetrahedron Letters, vol. 31, No. 3, pp. 335-338, 1990.
Ogilvie et al., "Synthesis of a Thymidine Dinucleotide Analogue Containing an Internucleotide Silyl Linkage", Tetrahedon Letters, vol. 26, No. 35, pp. 4159-4162, 1985.
Cormier et al., "Synthesis of Hexanucleotide Analogues Containing Diisopropylsilyl Internucleotide Linkages", Nucleic Acids Research, vol. 16, No. 10, pp. 4583-4594, 1988.

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