STUDIES ON OLIGONUCLEOTIDES CONTAINING POSITIVELY CHARGED BASES

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The overall aim of this project is to determine the stability of triplex DNAs formed between antigene oligodeoxynucleotides containing positively charged bases and duplex DNA targets. The ability of the charged bases, within the triplex, to interact with the different Watson-Crick base pair combinations will also be determined. Antigene oligodeoxynucleotides containing thymidine (T), cytidine (C), and other modified deoxynucleosides including ones possessing positively charged bases such as 3-methyldeoxycytidine (MdC+) will be synthesized. Target duplex DNA will also be synthesized such that one strand of the DNA will be purine- rich containing one or only a few pyrimidine interruptions and the other will be pyrimidine-rich. The stabilities of these triplexes will be primarily determined by ultraviolet (uv) melting studies. The antigene oligonucleotides and duplex DNA targets will be synthesized using standard phosphoramidite [1] chemistry and a DNA synthesizer. This study will also include the synthesis and investigation of the intramolecular stacking interaction occurring in dinucleoside monophosphates and trinucleoside diphosphates incorporated with the positively charged nucleoside, 3- methylcytidine. Finally, the zwitterionic 5'-5' dinucleoside monophosphate will be tested as a potential vehicle for the introduction of antiviral dideoxynucleosides as the 5'-nucleotide.