Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer

被引：41

作者：

Jenkins, Lisa M. Miller ^{[1
]}

Ott, David E. ^{[2
]}

Hayashi, Ryo ^{[1
]}

Coren, Lori V. ^{[2
]}

Wang, Deyun ^{[3
]}

Xu, Qun ^{[3
]}

Schito, Marco L. ^{[1
]}

Inman, John K. ^{[4
]}

Appella, Daniel H. ^{[3
]}

Appella, Ettore ^{[1
]}

机构：

[1] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA

[2] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA

[3] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA

[4] NIAID, Bethesda, MD 20892 USA

来源：

NATURE CHEMICAL BIOLOGY | 2010年 / 6卷 / 12期

基金：

美国国家卫生研究院;

关键词：

VIRAL NUCLEOCAPSID PROTEIN; DRUG-RESISTANCE; INHIBITORS; SPECIFICITY; THIOESTERS; INFECTION; TARGET;

D O I：

10.1038/NCHEMBIO.456

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：887 / 889

页数：3

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