Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir

J Med Chem. 2008 Oct 23;51(20):6599-603. doi: 10.1021/jm800283k. Epub 2008 Sep 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carbamates / chemistry*
  • Carbamates / metabolism*
  • Carbamates / pharmacology
  • Darunavir
  • Furans
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / metabolism*
  • HIV Protease Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • Kinetics
  • Models, Molecular
  • Molecular Structure
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism*
  • Sulfonamides / pharmacology


  • Carbamates
  • Furans
  • HIV Protease Inhibitors
  • Sulfonamides
  • amprenavir
  • Darunavir