Peptide substrates and inhibitors of the HIV-1 protease

Biochem Biophys Res Commun. 1989 Mar 15;159(2):420-5. doi: 10.1016/0006-291x(89)90008-9.


Oligopeptides containing the consensus retroviral protease cleavage sequence Ser/Thr-X-Y-Tyr/Phe-Pro are substrates for purified recombinant HIV-1 protease with Km's in the millimolar range. The minimum sequence containing the consensus pentapeptide which serves as a good substrate is a heptapeptide spanning the P4-P3' residues. Substitution of reduced Phe-Pro or Tyr-Pro dipeptide isosteres or the statine analog 3-hydroxy-4-amino-5-phenylpentanoic acid for the scissile dipeptide afforded inhibitors of HIV-1 protease with Ki values in the micromolar range, three orders of magnitude better in affinity than the corresponding substrates. Inhibitors of HIV-1 protease may provide a novel and potentially useful therapeutic approach to the treatment of acquired immune deficiency syndrome (AIDS).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Endopeptidases / metabolism
  • HIV Protease
  • Hydrolysis
  • Kinetics
  • Molecular Sequence Data
  • Oligopeptides / chemical synthesis
  • Oligopeptides / metabolism*
  • Protease Inhibitors*
  • Recombinant Proteins / metabolism
  • Retroviridae Proteins / metabolism
  • Substrate Specificity


  • Oligopeptides
  • Protease Inhibitors
  • Recombinant Proteins
  • Retroviridae Proteins
  • Endopeptidases
  • HIV Protease