title: Peptides containing acylated C-terminal gem diamines: novel irreversible inactivators of the cysteine and serine proteinases.
abstract: This study reports on the synthesis of peptides containing C-terminal acylated gem-diamines and their utilization for the preparation of irreversible inactivators of the serine and cysteine proteinases. We have succeeded in obtaining an inhibitor Acetyl-Val-Pro-g-Val-CO-O-C(6)H(4)-NO(2) of neutrophil and pancreatic elastases that functions in a time-dependent manner, indicative of the action of an irreversible inactivator, functioning, most probably, through the formation of a long-lived acyl enzyme intermediate. In addition, we have demonstrated the irreversible inhibition of the cysteine proteinase bovine cathepsin B, by chloroacetyl and bromoacetyl derivatives of a dipeptide gem-diamine, Cbz-Phe-g-Ala-CO-CH(2)Hal (Hal = Br, Cl).
authors.affiliation: The School of Pharmacy, McClay Research Centre, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. b.gilmore@qub.ac.uk
authors.forename: B F
authors.initials: BF
authors.lastname: Gilmore
authors.forename: J F
authors.initials: JF
authors.lastname: Lynas
authors.forename: P
authors.initials: P
authors.lastname: Harriott
authors.forename: A
authors.initials: A
authors.lastname: Healy
authors.forename: B
authors.initials: B
authors.lastname: Walker
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D002417:Cattle; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003959:Diamines / Q000032:analysis / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014520:Urethane / Q000031:analogs & derivatives*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D003959:Diamines; D004151:Dipeptides; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D014520:Urethane; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D002401:Cathepsin B