STUDIES ON OLIGONUCLEOTIDES CONTAINING POSITIVELY CHARGED BASES

含正电荷碱基寡核苷酸的研究

• 批准号: 6239889
• 负责人: NORMAN S KONDO
• 金额: $ 16.13万
• 依托单位: UNIVERSITY OF THE DISTRICT OF COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6239889
• 关键词: antineoplastics; antiviral agents; chemical stability; chemical structure function; chemical synthesis; cytidine; drug screening /evaluation; high performance liquid chromatography; intermolecular interaction; mass spectrometry; nucleobase; oligonucleotides; physical chemical interaction

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.

本项目的总体目标是确定三重稳定性 含有阳性的抗基因寡脱氧核苷酸之间形成的DNA 带电碱基和双链体DNA靶。 带电碱基的能力， 在三链体中，与不同的沃森-克里克碱基对相互作用， 组合也将被确定。 抗基因寡脱氧核苷酸 含有胸苷（T）、胞苷（C）和其他修饰的 脱氧核苷，包括具有带正电荷的碱基的脱氧核苷， 因为3-甲基脱氧胞苷（MdC+）将被合成。 靶双链DNA 也会被合成，使得DNA的一条链是嘌呤， 富含一个或仅几个嘧啶中断， 会富含嘧啶 这些三链体的稳定性将是 主要通过紫外线（UV）熔化研究确定。 抗基因 寡核苷酸和双链体DNA靶标将使用标准的 亚磷酰胺[1]化学和DNA合成仪。 本研究还将 包括分子内堆积的合成和研究 单磷酸二核苷和三核苷相互作用 与带正电荷的核苷结合的二磷酸，3- 甲基胞苷 最后，两性离子5 '-5'二核苷 一磷酸盐将作为引入的潜在载体进行测试 抗病毒的双脱氧核苷作为5 '-核苷酸。