title: Synthetic peptides as substrates and inhibitors of a retroviral protease.
abstract: Processing of the gag and pol gene precursor proteins of retroviruses is essential for infectivity and is directed by a viral protease that is itself included in one of these precursors. We demonstrate here that small synthetic peptides can be used as both model substrates and inhibitors to investigate the specificity and molecular parameters of the reaction. The results indicate that a peptide that extends five amino acids but not three amino acids in both directions from a known cleavage site is accurately hydrolyzed by the protease of avian sarcoma-leukosis virus. Substitutions of the amino acids to either side of the peptide bond to be cleaved affect the ability of the peptide (as well as a larger precursor protein) to serve as a substrate. The specificity is more stringent for the amino acid that will become the carboxyl end after cleavage. Some substitutions produced peptides that were not cleaved but could act as inhibitors of cleavage of a susceptible peptide. Thus, small model substrates may be used to explore both the binding and catalytic properties of these important proteases.
authors.affiliation: Department of Molecular Oncology, Roche Institute of Molecular Biology, Nutley, NJ 07110.
authors.forename: M
authors.initials: M
authors.lastname: Kotler
authors.forename: R A
authors.initials: RA
authors.lastname: Katz
authors.forename: W
authors.initials: W
authors.lastname: Danho
authors.forename: J
authors.initials: J
authors.lastname: Leis
authors.forename: A M
authors.initials: AM
authors.lastname: Skalka
mesh_terms: D001355:Alpharetrovirus / Q000201:enzymology; D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D007700:Kinetics; D009842:Oligopeptides; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D012190:Retroviridae / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D009842:Oligopeptides; D011480:Protease Inhibitors; D010447:Peptide Hydrolases