The Lossen rearrangement in biological systems. Inactivation of leukocyte elastase and alpha-chymotrypsin by (dl)-3-benzyl-N-(methanesulfonyloxy) succinimide.
(dl)-3-Benzyl-N-(methanesulfonyloxy) succinimide 5 has been found to inactivate human leukocyte elastase and alpha-chymotrypsin efficiently and irreversibly. The kobsd/[I] values were 1170 and 9000 M-1 s-1 respectively. Porcine pancreatic elastase was not inhibited by 5. Compound 5 may constitute the first example of a mechanism-based inhibitor of a serine proteinase that appears to exert its effect via an unprecedented enzyme-induced Lossen rearrangement.
D001665:Binding Sites; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013388:Succinimides; C051109:3-benzyl-N-(methanesulfonyloxy)succinimide; D002918:Chymotrypsin; D010196:Pancreatic Elastase