Design, synthesis, and kinetic evaluation of a unique class of elastase inhibitors, the peptidyl .alpha.-ketobenzoxazoles, and the x-ray crystal structure of the covalent complex between porcine pancreatic elastase and Ac-Ala-Pro-Val-2-benzoxazole

Peptidyl α-ketobenzoxazoles 1 and 2 are potent, competitive, reversible inhibitors or the serine proteinases HLE and PPE. These inhibitors were designed to inactivate the enzyme by interacting with both the serine hydroxyl group and the histidine imidazole ring or the catalytic triad. The X-ray crystal structure determination of 2 bound to PPE confirms the covalent attachment or the inhibitor's carbonyl carbon atom to the hydroxyl group or the active site Ser-195. The nitrogen atom or the benzoxazole ring partiapates in a hydrogen-bonding interaction with His-57