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

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).

authors

• Meek, Thomas

published proceedings

• Biochem Biophys Res Commun

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., ... Metcalf, B. W.

citation count

• 159

complete list of authors

• Moore, ML||Bryan, WM||Fakhoury, SA||Magaard, VW||Huffman, WF||Dayton, BD||Meek, TD||Hyland, L||Dreyer, GB||Metcalf, BW

publication date

• January 1989

publisher

• Elsevier  Publisher

published in

• Biochemical and Biophysical Research Communications  Journal

keywords

• Amino Acid Sequence
• Endopeptidases
• Hiv Protease
• Hydrolysis
• Kinetics
• Molecular Sequence Data
• Oligopeptides
• Protease Inhibitors
• Recombinant Proteins
• Retroviridae Proteins
• Substrate Specificity

Digital Object Identifier (DOI)

• 10.1016/0006-291x(89)90008-9

start page

• 420

end page

• 425

volume

• 159

issue

• 2

URL

• http://dx.doi.org/10.1016/0006-291x(89)90008-9