Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer.
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ABSTRACT:
SUBMITTER: Miller Jenkins LM
PROVIDER: S-EPMC2997617 | biostudies-literature | 2010 Dec
REPOSITORIES: biostudies-literature
Publications
Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer.
Miller Jenkins Lisa M LM Ott David E DE Hayashi Ryo R Coren Lori V LV Wang Deyun D Xu Qun Q Schito Marco L ML Inman John K JK Appella Daniel H DH Appella Ettore E
Nature chemical biology 20101017 12
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. ...[more]
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