STUDIES ON OLIGONUCLEOTIDES CONTAINING POSITIVELY CHARGED BASES

本项目的总体目标是确定三联体的稳定性 含正链的反义寡核苷酸之间形成的DNA 带电碱基和双重DNA靶标。带电碱基的能力， 在三链内，与不同的Watson-Crick碱基对相互作用 还将确定组合。反义寡核苷酸 含有胸苷(T)、胞苷(C)等修饰 脱氧核苷，包括具有正电荷碱基的脱氧核苷 将合成3-甲基脱氧胞苷(MDC+)。靶向双链DNA 也会被合成成DNA的一条链是嘌呤- 富含一个或只有几个嘧啶中断和另一个 将是富含嘧啶的。这些三联体的稳定性将是 主要由紫外线(UV)熔融研究确定。抗基因 寡核苷酸和双链DNA靶标将用标准的 亚磷酰胺[1]化学和DNA合成器。这项研究还将 包括分子内堆积的合成和研究 二核苷一磷酸与三核苷的相互作用 与带正电荷的核苷结合的二磷酸盐，3- 甲基胞苷。最后，两性离子5‘-5’二核苷 单磷酸盐将作为潜在的引入载体进行测试 作为5‘-核苷酸的抗病毒双脱氧核苷。

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.