The long range goal of this project is to prepare defined sequence oligodeoxyribonucleotides and certain oligonucleoside analogues covalently linked to intercalating drugs for use as anti-viral agents in the treatment of Acquired Immune Deficiency Syndrome. A new type of solid support for oligonucleotide synthesis will be developed. This support incorporates a novel linkage between the silica matrix and the growing oligonucleotide chain which allows for release of a fully protected synthetic oligomer. The use of this solid support will permit selective derivatization of either the 5' or 3' ends of the oligonucleotide prior to removal of the pure and pyrimidine base protecting groups. Oligonucleoside analogues containing non-ionic carbamate internucleoside linkages will be investigated. Both deoxyribonucleoside and ribonucleoside carbamate-linked analogues will be prepared. The interaction of these nucleic acid analogues with DNA and RNA sequences will be analyzed. This study will focus on developing chemically stable analogues with the necessary base pairing and solubility properties needed for therapeutic uses.
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