title: Potent and selective inactivation of cysteine proteinases with N-peptidyl-O-acyl hydroxylamines.
abstract: A series of N-peptidyl-O-acyl hydroxylamines was synthesized and tested as inactivators of cysteine proteinases. Depending on the structure of the peptidyl residue of the inhibitors, rapid and complete irreversible inactivation of the lysosomal cathepsins, B, L and S, may be achieved. The most effective inhibitors display second-order rate constants of the inactivation in the range 10(5)-10(6) M-1.s-1. By contrast, the activity of the aminoendopeptidase cathepsin H is only negligibly affected by the N-terminal-protected peptidyl inhibitors.
authors.affiliation: Institute of Biochemistry, Medical Faculty, Martin-Luther-University, Halle, German Democratic Republic.
authors.forename: D
authors.initials: D
authors.lastname: Brömme
authors.forename: A
authors.initials: A
authors.lastname: Schierhorn
authors.forename: H
authors.initials: H
authors.lastname: Kirschke
authors.forename: B
authors.initials: B
authors.lastname: Wiederanders
authors.forename: A
authors.initials: A
authors.lastname: Barth
authors.forename: S
authors.initials: S
authors.lastname: Fittkau
authors.forename: H U
authors.initials: HU
authors.lastname: Demuth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002403:Cathepsins / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006898:Hydroxylamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D015842:Serine Proteinase Inhibitors
chemical_list: D015853:Cysteine Proteinase Inhibitors; D006898:Hydroxylamines; D010455:Peptides; D015842:Serine Proteinase Inhibitors; D002403:Cathepsins; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4