Reaction of Azapeptides with Human Leukocyte Elastase and Porcine Pancreatic Elastase. New Inhibitors and Active Site Titrants

The reaction of a series of azapeptides with porcine pancreatic (PP) elastase and human leukocyte (HL) elastase has been studied and a series of new inhibitors and active site titrants were found for both PP elastase and HL elastase. Azapeptide p-nitrophenyl esters acylate both HL and PP elastase to form stable acylenzymes, which can be used for crystallographic studies. We have investigated the effect of a P1, P2, or P3 aza-amino acid residue on the reactivity of azapeptides with elastase. We have also studied the effect of changing the nature of the P1' leaving group and other portions of azapeptide structure. N-Acetyl-L-alanyl-L-alanyl-alpha-azaalanine p-nitrophenyl ester, N-acetyl-L-alanyl-L-alanyl-alpha-azanorleucine p-nitrophenyl ester, and N-acetyl-L-alanyl-L-alanyl-alpha-azanorvaline p-nitrophenyl ester are suitable titrants for either PP or HL elastase.