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.

该项目的总体目的是确定三元的稳定性 在含有积极的抗基因寡脱氧核苷酸之间形成的DNA 带电的碱基和双链DNA靶标。 充电基地的能力， 在三元中，与不同的沃森 - 克里克基对互动 还将确定组合。 抗基因寡脱氧核苷酸 含有胸苷（T），胞苷（C）和其他修饰 脱氧核苷，包括具有带正电碱基的脱氧核苷 将合成3-甲基氧基胞苷（MDC+）。 目标双链DNA 还将合成，以使DNA的一链将是嘌呤 富含一个或仅几个嘧啶的中断，另一个包含少数嘧啶的中断 将是富含嘧啶的。 这些三元的稳定性将是 主要由紫外线（UV）熔融研究确定。 抗基因 寡核苷酸和双链DNA靶标将使用标准合成 磷酸胺[1]化学和DNA合成剂。 这项研究也将 包括分子内堆叠的合成和研究 在二核苷单磷酸盐和三核苷中发生的相互作用 与带正电核苷的二磷酸盐掺入3- 甲基胞苷。 最后，zwitterion 5'-5'dinucleoside 单磷酸将作为引入的潜在工具进行测试 抗病毒二氧核苷作为5'-核苷酸。