Amino acids and peptides. XXII. Synthesis of substrates and inhibitors of human leukocyte cathepsin G.

Suc-Tyr-Leu-Phe-pNA is a good substrate for human leukocyte cathepsin G and achymotrypsin but not for human leukocyte elastase(HLE).However,Suc-Tyr-D-Leu-D-Phe-pNA inhibited not only cathepsin G and a-chymotrypsin but also HLE(Ki values,1.1,0 .94 and0.16mM, respectively).The p-nitroanilide(pNA)moiety of Suc-Tyr—Leu—Phe-pNA and Suc-Tyr-D-Leu-DPhe-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 a-chymotrypsin was studied .Suc-Tyr-Leu-Phe-BZA inhibited HLE, cathepsin G and a-chymotrypsin with Ki values of 0 .027,0.1and0.01mM,respectively.