ACRIDINES LINKED TO OLIGONUCLEOTIDES AS ANTI-HIV AGENTS

点击翻译按钮获取中文摘要

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).