Peptide substrates and inhibitors of the HIV-1 protease
Biochemical and Biophysical Research CommunicationsPublished 1 March 1989
Michael L. Moore, William M. Bryan, Stephen A. Fakhoury, Victoria W. Magaard, William F. Huffman, Brian D. Dayton
Citations161
SJR quartileQ2
SJR score0.75
SNIP0.56
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TL;DR
Inhibitors of HIV-1 protease may provide a novel and potentially useful therapeutic approach to the treatment of acquired immune deficiency syndrome (AIDS), three orders of magnitude better in affinity than the corresponding substrates.
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).
Keywords
Immunology and MicrobiologyMedicine
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