小分子通过重复的细胞内酰基转移使 HIV-1 NCp7 失活。
Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer.
机构信息
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
出版信息
Nat Chem Biol. 2010 Dec;6(12):887-9. doi: 10.1038/nchembio.456. Epub 2010 Oct 17.
Abstract
The zinc fingers of the HIV-1 nucleocapsid protein, NCp7, are prime targets for antiretroviral therapeutics. Here we show that S-acyl-2-mercaptobenzamide thioester (SAMT) chemotypes inhibit HIV by modifying the NCp7 region of Gag in infected cells, thereby blocking Gag processing and reducing infectivity. The thiol produced by SAMT reaction with NCp7 is acetylated by cellular enzymes to regenerate active SAMTs via a recycling mechanism unique among small-molecule inhibitors of HIV.
摘要
HIV-1 核衣壳蛋白 NCp7 的锌指是抗逆转录病毒治疗的主要靶点。在这里，我们表明 S-酰基-2-巯基苯甲酰胺硫酯 (SAMT) 化学型通过修饰感染细胞中 Gag 的 NCp7 区域来抑制 HIV，从而阻断 Gag 加工并降低感染性。SAMT 与 NCp7 反应产生的硫醇被细胞酶乙酰化，通过一种在 HIV 小分子抑制剂中独特的循环机制再生活性 SAMTs。
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