Solution Kinetics Measurements Suggest HIV-1 Protease Has Two Binding Sites for Darunavir and Amprenavir

Citations Over TimeTop 16% of 2008 papers

Abstract

Darunavir, a potent antiviral drug, showed an unusual second binding site on the HIV-1 protease dimer surface of the V32I drug resistant mutant and normal binding in the active site cavity. Kinetic analysis for wild type and mutant protease showed mixed-type competitive-uncompetitive inhibition for darunavir and the chemically related amprenavir, while saquinavir showed competitive inhibition. The inhibition model is consistent with the observed second binding site for darunavir and helps to explain its antiviral potency.

Related Papers

• → Inhibition of HIV‐2 Protease by HIV‐1 Protease Inhibitors in Clinical Use(2008)109 cited
• → A Contribution to the Drug Resistance Mechanism of Darunavir, Amprenavir, Indinavir, and Saquinavir Complexes with HIV-1 Protease Due to Flap Mutation I50V: A Systematic MM–PBSA and Thermodynamic Integration Study(2013)77 cited
• → Prevalence, Mutation Patterns, and Effects on Protease Inhibitor Susceptibility of the L76V Mutation in HIV-1 Protease(2010)44 cited
• → Resistance to HIV Protease Inhibitors: Mechanisms and Clinical Consequences(2004)29 cited
• → Ongoing trials in HIV protease inhibitors(2000)7 cited