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

@article{Jenkins2010SmallmoleculeIO,
  title={Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer.},
  author={Lisa M. Miller Jenkins and David E. Ott and Ryo Hayashi and Lori V. Coren and Deyun Wang and Qun Xu and Marco L. Schito and John K. Inman and Daniel H. Appella and Ettore Appella},
  journal={Nature chemical biology},
  year={2010},
  volume={6 12},
  pages={887-9}
}
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.