Hazuda D J, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler J A, Espeseth A, Gabryelski L, Schleif W, Blau C, Miller M D
Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA.
Science. 2000 Jan 28;287(5453):646-50. doi: 10.1126/science.287.5453.646.
Integrase is essential for human immunodeficiency virus-type 1 (HIV-1) replication; however, potent inhibition of the isolated enzyme in biochemical assays has not readily translated into antiviral activity in a manner consistent with inhibition of integration. In this report, we describe diketo acid inhibitors of HIV-1 integrase that manifest antiviral activity as a consequence of their effect on integration. The antiviral activity of these compounds is due exclusively to inhibition of one of the two catalytic functions of integrase, strand transfer.
整合酶对于1型人类免疫缺陷病毒（HIV-1）的复制至关重要；然而，在生化分析中对分离出的该酶的有效抑制尚未以与整合抑制相一致的方式轻易转化为抗病毒活性。在本报告中，我们描述了HIV-1整合酶的二酮酸抑制剂，这些抑制剂因其对整合的影响而表现出抗病毒活性。这些化合物的抗病毒活性完全归因于对整合酶两种催化功能之一——链转移的抑制。
