title: Evaluation of dipeptide alpha-keto-beta-aldehydes as new inhibitors of cathepsin S.
abstract: A series of dipeptidyl alpha-keto-beta-aldehydes (glyoxals), prepared by solid-/solution-phase chemistries, were assessed for their inhibitory activity against cathepsin S, a lysosomal cysteine protease implicated in a number of important pathophysiological processes. The inhibitor Cbz-Phe-Leu-COCHO, which exhibits slow-binding kinetic characteristics, was found to be almost 400-fold more selective for cathepsin S (K(i) = 0.185 nM) than for cathepsin B (76 nM) and is, to our knowledge, the most potent, reversible, synthetic cathepsin S inhibitor reported to date.
authors.affiliation: Division of Biomedicinal Chemistry, School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 79 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, United Kingdom. brian.walker@qub.ac.uk
authors.forename: B
authors.initials: B
authors.lastname: Walker
authors.forename: J F
authors.initials: JF
authors.lastname: Lynas
authors.forename: M A
authors.initials: MA
authors.lastname: Meighan
authors.forename: D
authors.initials: D
authors.lastname: Brömme
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology*; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D004151:Dipeptides / Q000737:chemistry; D005069:Evaluation Studies as Topic; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D000447:Aldehydes; D004151:Dipeptides; D011480:Protease Inhibitors; D002403:Cathepsins; C028217:cathepsin S