The inhibition of human neutrophil elastase and cathepsin G by peptidyl 1,2-dicarbonyl derivatives

Abstract

Neutrophil elastase and cathepsin G are serine proteases that can damage connective tissue and trigger other pathological reactions. Compounds containing a peptide sequence to impart specificity and bearing an α-dicarbonyl unit (α-diketone or α-keto ester) at the carboxy terminus are potent inhibitors of the neutrophil serine proteases (human neutrophil elastase: R-Val-COCH 3, K i = 0.017 μM; R-Val-COOCH 3, K i = 0.002 μM; human neutrophil cathepsin G: R-Phe-COCH 3, K i = 0.8 μM; R-Phe-COOCH 3, K i = 0.44 μM; R = N-(4-[(4-chlorophenyl)sulfonylaminocarbonyl]phenylcarbonyl)ValylProlyl).