FEBS Letters · 1990 · 50 citations · 10 references
Life SciencesBiochemistryMolecular BiologyEnzymologyMolecular VirologyVirologyEnzyme FunctionEnzyme KineticsPeptide ChemistryProtein ChemistryProtein StructureProteolytic EnzymesAspartic ProteasesEnzymatic Hydrolysis Of ProteinsPh DependenceProtease Cleavage SpecificityProtease KineticsProtease SelectivitySynthetic Peptide CharacterizationViral Protease Specificity
A series of synthetic, chromogenic substrates for HIV-1 proteinase with the general structure Ala-Thr-His-Xaa-Yaa-Zaa*Nph-Val-Arg-Lys-Ala was synthesised with a variety of residues introduced into the Xaa, Yaa and Zaa positions. Kinetics parameters for hydrolysis of each peptide by HIV-1 proteinase at pH 4.7, 37 degrees C and u = 1.0 M were measured spectrophotometrically and/or by reverse phase FPLC. A variety of residues was found to be acceptable in the P3 position whilst hydrophobic/aromatic residues were preferable in P1. The nature of the residue occupying the P2 position had a strong influence on kcat (with little effect on Km); beta-branched residues Val or Ile in this position resulted in considerably faster peptide hydrolysis than when e.g. the Leu-containing analogue was present in P2.
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Rational Design of Peptide-Based HIV Proteinase Inhibitors
Noel A. Roberts, Joseph A. Martin, Derek Kinchington et al. · Science · 1990 · 925 citations
Peptides Chemistry, Structure and Biology
Jean Rivier, Garland R. Marshall · 1990 · 510 citations