Peptide substrates and inhibitors of the HIV-1 protease Academic Article uri icon

abstract

  • 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).

altmetric score

  • 6

author list (cited authors)

  • Moore, M. L., Bryan, W. M., Fakhoury, S. A., Magaard, V. W., Huffman, W. F., Dayton, B. D., ... Debouck, C.

citation count

  • 149

publication date

  • March 1989