ACRIDINES LINKED TO OLIGONUCLEOTIDES AS ANTI-HIV AGENTS

该提案要求提供资金来合成抗HTLV-III/LAV/HIV 针对逆转录病毒RNA上特定序列的药物 模板。具体地说，十脱氧核苷酸将是 合成并通过不同的链结连接到吖啶类化合物 5‘-磷酸、3’-磷酸以及5‘-和3’- 磷酸基团。不同长度和不同长度的系绳 将使用各种功能。寡聚脱氧核糖核苷酸是 针对HTLV-III/LAV/HIV的重要序列而设计 吉恩。吖啶类化合物有望与该基因相互作用，并 稳定绑定。 寡聚脱氧核糖核苷酸及其吖啶结合物将 被提供给中央核心用于测试和物理化学 学习。这些研究有望产生新的抗艾滋病药物 代理，并提供有关导致 为了最活跃的人。此外，不同的是 寡核苷酸将提供关于哪种基因的信息 在HTLV-III中，这些药物最容易被取代。此外，这一点 该项目具有普遍意义，因为它将揭示 将药物和其他制剂导向特定核素的方法 酸序列(基因)。

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).