EFFECT OF OXIDATION OF METHIONINE IN A PEPTIDE SUBSTRATE FOR HUMAN ELASTASES - MODEL FOR INACTIVATION OF ALPHA-1-PROTEASE INHIBITOR

Human α1-protease inhibitor which is an important plasma protein, contains a methionine residue at its reactive site. A model synthetic peptide substrate, succinyl-L-alanyl-L-alanyl-L-prolyl-L-methionine p-nitroanilide, has been employed to study the effect of oxidation of methionine on the rate of hydrolysis of this substrate by human elastases. The methionine sulfoxide derivative obtained by mild oxidation of this substrate is hydrolyzed by pancreatic elastase 2 and leukocyte elastase at rates that are 5% and 0.3% of the rates measured for hydrolysis of the parent compound by the respective enzymes. These results suggest that oxidation of the active site methionine residue of human α1-protease inhibitor may decrease the rate of reaction of pancreatic or leukocyte elastase with this inhibitor. © 1979.