title: Acyloxybenzyl halides, inhibitors of elastases.
abstract: 3-Benzyl-6-chloromethyl-3,4-dihydrocoumarin inhibits human leucocyte elastase (HLE) and porcine pancreatic elastase (PPE) through a mechanism-based process characterized by the following apparent enzyme-inhibitor dissociation constants, Ki, and limiting inactivation rate constants k2: 200 microM (HLE), 69 microM (PPE) and 5.10(-2) s-1 (HLE), 17.7.10(-2) s-1 (PPE) at pH 8.0, 37 degrees C. Bis(4-acyloxyphenyl)methane derivatives with a benzylic halogen as potential leaving group have also been synthesized and studied. They transiently inactivate PPE and HLE through the formation of an acyl-enzyme.
authors.affiliation: Laboratoire de Bioactivation des Peptides, Institut Jacques Monod, Thiais, France.
authors.forename: A C
authors.initials: AC
authors.lastname: Vilain
authors.forename: V
authors.initials: V
authors.lastname: Okochi
authors.forename: I
authors.initials: I
authors.lastname: Vergely
authors.forename: M
authors.initials: M
authors.lastname: Reboud-Ravaux
authors.forename: J P
authors.initials: JP
authors.lastname: Mazaleyrat
authors.forename: M
authors.initials: M
authors.lastname: Wakselman
mesh_terms: D000818:Animals; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000097:blood; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D003374:Coumarins; D007202:Indicators and Reagents; D011480:Protease Inhibitors; C058018:3,4-dihydro-3-benzyl-6-chloromethylcoumarin; D010196:Pancreatic Elastase