FUNCTIONS AND INHIBITION OF HIV POLYMERASE

HIV聚合酶的功能和抑制

• 批准号: 2413365
• 负责人: Lorna RODRIGUEZ-RODRIGUEZ
• 金额: $ 9.01万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2413365
• 关键词: DNA primers; RNA directed DNA polymerase; cis platinum compound; exonuclease; genetic manipulation; genetic transcription; human immunodeficiency virus; nucleic acid sequence; nucleoside triphosphate; protein structure function; reverse transcriptase inhibitors; ribonuclease III; virus genetics

Retrovirus reverse transcriptases (RT) catalyze a reaction called transfer synthesis, whereby a DNA primer is moved form one viral template to another. The reaction is essential for viral replication, and likely an important step in recombination. It is probable that this type of reaction, when it occurs between internal regions of the viral chromosome, contributes to diversity in the viral genome, improving viral survival. We intent to understand and eventually prevent internal strand transfer from occurring in vivo, since it may be one of the features that improves virulence. A strand transfer assay in vitro will be used to measure the capacity of the reverse transcriptase to transfer DNA synthesis from a natural sequence donor template to an acceptor template. The role of template sequence and secondary structure, and of RNA cleavage, in the strand transfer reaction will be tested. Effects of specific alterations in gap size produced in the RNA template, the size of specifically introduced hairpin loops, and degree of homology between donor and acceptor templates on the efficiency of strand transfer will be examined. The effect of covalent modifications to the donor RNA forming cisplatin adducts will also be determined. Clinically relevant experiments will be done determining the effects of BI-RG-587 and its analogues on processive primer elongation necessary for strand transfer. In summary, the experiments are designed to determine the characteristic of the templates, RT and reaction conditions that favor the internal strand transfer reaction.

逆转录病毒逆转录酶（RT）催化一种叫做