FAT AND SLIM NUCLEOSIDES AND NUCLEOTIDES

脂肪和细长的核苷和核苷酸

• 批准号: 2733233
• 负责人: Ramachandra S Hosmane
• 金额: $ 22.33万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-15 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733233
• 关键词: adenosine deaminase; aminohydrolases; antiAIDS agent; antineoplastics; antiviral agents; chemical structure; conformation; drug design /synthesis /production; enzyme inhibitors; heterocyclic compounds; murine leukemia virus; nucleic acid structure; nucleoside analog; nucleosides; nucleotide analog; phosphorylases

Synthesis, chemistry and biochemistry of a family of "fat" nucleosides and nucleotides possessing the following 5:7-fused heterocyclic base systems will be studied: I) imidazo(4,5,e)(1,3,4)triazepine; II) imidazo(4,5-e)(1,4)diazepine; and III) imidazo(4,5,d)(1,3)diazepine. The novel rearrangement discovered in the heterocyclic system of category I will be further explored for wide synthetic utility. The mono- and diphosphate derivatives of nucleosides of category II will be prepared. The diphosphates will be polymerized by using the enzyme polynucleotide phosphorylase and the resulting homopolymer templates will be evaluated for substrate/inhibitory activity against Moloney murine leukemia virus (M-MuLV) reverse transcriptase. These studies will be extended to "fat" nucleoside/nucleotide systems of categories I & III. The target and intermediate nucleosides and heterocycles will be screened for potential antitumor activity by the National Cancer Institute. The ongoing collaborative arrangements with Professor E. De Clercq of Katholieke University, Leuven, Belgium will enable testing of the above compounds for antiviral activity in a broad range of viral assay systems. Preliminary studies on the 5:8-fused heterocylic systems will be continued. As a secondary goal, double helical complexes will be prepared by pairing the above "fat" nucleotide homopolymers with appropriate pyrimidine counterparts, and investigated for stability, stacking interactions and conformational characteristics.

脂肪族的合成、化学和生物化学 具有以下5：7-融合的核苷和核苷酸 将研究基于杂环体系：I） 咪唑并（4，5-e）（1，3，4）三氮杂; 和III）咪唑并（4，5，d）（1，3）二氮杂。 小说改编 在I类杂环体系中发现的，将进一步 探索广泛的合成用途。 单磷酸和二磷酸 将制备II类核苷的衍生物。 的 二磷酸盐将通过使用酶聚合， 多核苷酸磷酸化酶和所得的均聚物 将评价模板的底物/抑制活性 抗莫洛尼鼠白血病病毒（M-MuLV）逆转 录酶 这些研究将扩展到“脂肪” 第I类和第III类的核苷/核苷酸系统。 目标 并筛选中间体核苷和杂环 潜在的抗肿瘤活性。 目前与E教授的合作安排。 De 比利时鲁汶Katholieke大学的职员将使 在广泛范围内测试上述化合物的抗病毒活性 一系列病毒检测系统。 5：8-融合蛋白的初步研究 杂环系统将继续。 作为次要目标， 双螺旋复合物将通过配对上述 “脂肪”核苷酸均聚物与适当的嘧啶 同行，并调查了稳定性，堆叠相互作用 和构象特征。