Amino Acids and Peptides. XXII. Synthesis of Substrates and Inhibitors of Human Leukocyte Cathepsin G

Abstract

Suc-Tyr-Leu-Phe-pNA is a good substrate for human leukocyte cathepsin G and α-chymotrypsin but not for human leukocyte elastase (HLE). However, Suc-Tyr-D-Leu-D-Phe-pNA inhibited not only cathepsin G and α-chymotrypsin but also H LE (Ki values, 1.1, 0.94 and 0.16 mM, respectively). The p-nitroanilide (pNA) moiety of Suc-Tyr-Leu-Phe-pNA and Suc-Tyr-D-Leu-D-Phe-pNA was substituted with p-benzoylaniline (BZA), p-acetylaniline (ACA), 4-benzylpiperidine (BPP) and 4-methylpiperidine (Pipe). The relationship between the structure and inhibitory effect on HLE, cathepsin G and α-chymotrypsin was studied. Suc-Tyr-Leu-Phe-BZA inhibited HLE, cathepsin G and a-chymotrypsin with Kivalues of 0.027, 0.1 and 0.01 mM, respectively. © 1988, The Pharmaceutical Society of Japan. All rights reserved.