ACRIDINES LINKED TO OLIGONUCLEOTIDES AS ANTI-HIV AGENTS

吖啶与寡核苷酸结合作为抗艾滋病毒药物

• 批准号: 3818746
• 负责人: STEPHEN BRYN
• 金额: --
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3818746
• 关键词: AIDS; acridines; aminoacridines; antiAIDS agent; antiviral agents; chemical binding; chemical conjugate; deoxyribopolynucleotide; drug design /synthesis /production; high performance liquid chromatography; human immunodeficiency virus 1; microorganism disease chemotherapy; nucleic acid sequence; nucleotide analog; phosphates; virus genetics

This proposal requests funds to synthesize anti-HTLV-III/LAV/HIV agents targeted to specific sequences on the retroviral RNA template. Specifically, dedecadeoxyribonucleotides will be synthesized and connected to acridines via various tethers to the 5'-phosphate, to the 3'-phosphate, and to both the 5'- and 3'- phosphate group. Tethers with different lengths and functionalities will be used. The oligodeoxyribonucleotides are designed to target important sequences of the HTLV-III/LAV/HIV gene. The acridines are expected to interact with this gene and stabilize the binding. The oligodeoxyribonucleotides and their acridine conjugates will be provided to the central core for testing and physico-chemical studies. These studies are expected to result in novel anti-AIDS agents and provide information on the type of linkage which leads to the most activity. In addition, the different oligodeoxyribonucleotides will provide information on which gene in HTLV-III is most succeptible to these agents. In addition, this project is of general significance since it will shed light on approaches to directing drugs and other agents to specific nucleic acid sequences (genes).

该提案要求资金合成抗HTLV-III/LAV/HIV 针对逆转录病毒RNA上特定序列的药物 模板。 具体而言，十氧核糖核苷酸将是 合成并通过各种系链与吖啶连接 5'-磷酸盐、3'-磷酸盐以及5'-和3'-磷酸盐 磷酸基团。 不同长度的系绳 将使用功能。 寡脱氧核糖核苷酸是 旨在针对 HTLV-III/LAV/HIV 的重要序列 基因。 预计吖啶会与该基因相互作用并且 稳定结合。 寡脱氧核糖核苷酸及其吖啶缀合物将 提供给中央核心进行测试和理化 研究。 这些研究预计将产生新的抗艾滋病药物 代理并提供有关导致的链接类型的信息 到最活跃的程度。 此外，不同的 寡脱氧核糖核苷酸将提供有关哪个基因的信息 HTLV-III 中的病毒对这些药物最敏感。 此外，这 该项目具有普遍意义，因为它将阐明 将药物和其他试剂导向特定核酸的方法 酸序列（基因）。