Substitution of proline with pipecolic acid at the scissile bond converts a peptide substrate of HIV proteinase into a selective inhibitor

Terry D. Copeland, Ewald M. Wondrak, Jozsef Tozser, Michael M. Roberts, Stephen Oroszlan

Research output: Contribution to journalArticle

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The nonapeptide H-Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-NH2 containing the retroviral Tyr-Pro cleavage site is a good substrate for the proteinase of human immunodeficiency viruses but it is not readily hydrolyzed by other nonviral proteinases including the structurally related pepsin-like aspartic proteinases. Replacing the Pro by L-pipecolic acid (2-piperidinecarboxylic acid) converted the substrate into an effective inhibitor of HIV-1 and HIV-2 proteinases with IC50 of ∼ 1 μM. This compound showed a high degree of selectivity in that it did not inhibit cathepsin D and renin.

Original languageEnglish
Pages (from-to)310-314
Number of pages5
JournalBiochemical and biophysical research communications
Issue number1
Publication statusPublished - May 31 1990


ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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