FAT AND SLIM NUCLEOSIDES AND NUCLEOTIDES

脂肪和细长的核苷和核苷酸

• 批准号: 2443252
• 负责人: Ramachandra S Hosmane
• 金额: $ 23.1万
• 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 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2443252
• 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”家族的合成，化学和生物化学 具有以下5：7融合的核苷和核苷酸 将研究杂环基本系统：i） Imidazo（4,5，E）（1,3,4）三泽； ii）Imidazo（4,5-E）（1,4）地西班平； 和iii）伊皮唑（4,5，d）（1,3）地西平。 新颖的重排 在类别的杂环系统中发现 探索用于广泛的合成效用。 单磷酸和双磷酸盐 将制备II类核苷的衍生物。 这 双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 将评估模板的底物/抑制活性 反对莫洛尼鼠白血病病毒（M-Mulv）反向 转录酶。 这些研究将扩展到“脂肪” I＆III类别的核苷/核苷酸系统。 目标 和中间核苷和杂环将筛选 国家癌症研究所的潜在抗肿瘤活性。 与E. de教授的持续合作安排 比利时鲁汶凯托利克大学的Clercq将启用 在广泛的 病毒测定系统范围。 对5：8融合的初步研究 杂环系统将继续。 作为次要目标， 双螺旋络合物将通过配对以上来制备 具有适当嘧啶的“脂肪”核苷酸均聚物 对应物，并进行了调查以稳定，堆叠相互作用 和构象特征。