Identification of broad-based HIV-1 protease inhibitors from combinatorial libraries.

ABSTRACT: Clinically approved inhibitors of the HIV-1 protease function via a competitive mechanism. A particular vulnerability of competitive inhibitors is their sensitivity to increases in substrate concentration, as may occur during virion assembly, budding and processing into a mature infectious viral particle. Advances in chemical synthesis have led to the development of new high-diversity chemical libraries using rapid in-solution syntheses. These libraries have been shown previously to be effective at disrupting protein-protein and protein-nucleic acid interfaces. We have screened 44000 compounds from such a library to identify inhibitors of the HIV-1 protease. One compound was identified that inhibits wild-type protease, as well as a drug-resistant protease with six mutations. Moreover, anal

SUBMITTER: Chang MW 

PROVIDER: S-EPMC3084599 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature