Acyloxybenzyl halides, inhibitors of elastases.
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.
Vilain
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AC
Laboratoire de Bioactivation des Peptides, Institut Jacques Monod, Thiais, France.
Okochi
V
V
Vergely
I
I
Reboud-Ravaux
M
M
Mazaleyrat
J P
JP
Wakselman
M
M
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
D003374:Coumarins; D007202:Indicators and Reagents; D011480:Protease Inhibitors; C058018:3,4-dihydro-3-benzyl-6-chloromethylcoumarin; D010196:Pancreatic Elastase