title: Peptide methyl ketones as reversible inhibitors of cysteine proteinases.
abstract: Peptide methyl ketones represent a new class of reversible, competitive cysteine proteinase inhibitor with little or no effect on serine proteinases. The affinity of the inhibitors to papain (EC 3.4.22.3), cathepsin B (EC 3.4.22.1) and cathepsin L (EC 3.4.22.15) depends on the peptide chain length and on side-chain effects. Variations in the P1 and P4 positions (terminology of Schechter and Berger) and their influence on the efficiency of the inhibitors have been investigated. The most effective inhibitors display inhibition constants in the micromolar range. In contrast to the endopeptidases papain and the cathepsins B and L, the aminoendopeptidase cathepsin H (EC 3.4.22.16) is not inhibited by N-acylated peptide methyl ketones but only by amino methyl ketones containing a free alpha-amino group. The endopeptidases are not affected by amino methyl ketones.
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, DDR.
authors.forename: D
authors.initials: D
authors.lastname: Brömme
authors.forename: B
authors.initials: B
authors.lastname: Bartels
authors.forename: H
authors.initials: H
authors.lastname: Kirschke
authors.forename: S
authors.initials: S
authors.lastname: Fittkau
mesh_terms: D000595:Amino Acid Sequence; D002403:Cathepsins / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010206:Papain / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007659:Ketones; D009842:Oligopeptides; D002403:Cathepsins; D010206:Papain