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, J. Tőzsér, Michael M. Roberts, Stephen Oroszlan

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

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
Volume169
Issue number1
DOIs
Publication statusPublished - May 31 1990

Fingerprint

HIV Protease
Proline
tyrosyl-proline
Peptide Hydrolases
Substitution reactions
Aspartic Acid Proteases
Cathepsin D
Peptides
HIV-2
Pepsin A
Substrates
Renin
Inhibitory Concentration 50
HIV-1
HIV
Viruses
pipecolic acid
1-(2-(3-methoxyphenyl)ethyl)phenoxy-3-(dimethylamino)-2-propanol
HIV protease nonapeptide substrate

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Substitution of proline with pipecolic acid at the scissile bond converts a peptide substrate of HIV proteinase into a selective inhibitor. / Copeland, Terry D.; Wondrak, Ewald M.; Tőzsér, J.; Roberts, Michael M.; Oroszlan, Stephen.

In: Biochemical and Biophysical Research Communications, Vol. 169, No. 1, 31.05.1990, p. 310-314.

Research output: Contribution to journalArticle

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