Analysis and characterization of dimerization inhibition of a multi-drug-resistant human immunodeficiency virus type 1 protease using a novel size-exclusion chromatographic approach.

ABSTRACT: Active-site inhibitors of HIV-1 PR (protease) block viral replication by preventing viral maturation. However, HIV-1 often develops resistance to active-site inhibitors through multiple mutations in PR and therefore recent efforts have focused on inhibiting PR dimerization as an alternative approach. Dimerization inhibitors have been identified using kinetic analysis, but additional characterization of the effect of these inhibitors on PR by physical methods has been difficult. In the present study, we identified a PR(MDR) (multi-drug-resistant HIV-1 PR) that was highly resistant to autoproteolysis. Using this PR and a novel size-exclusion chromatographic approach that incorporated fluorescence and MS detection, we were able to demonstrate inhibition of dimerization using P27 (peptide 27),

SUBMITTER: Davis DA 

PROVIDER: S-EPMC2748811 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature