AMINO-ACIDS AND PEPTIDES .37. SYNTHESIS OF STEREOISOMERIC NONAPEPTIDES CORRESPONDING TO SEQUENCE-41-49 OF EGLIN-C AND EXAMINATION OF THEIR INHIBITORY ACTIVITY AGAINST HUMAN-LEUKOCYTE CATHEPSIN-G AND ALPHA-CHYMOTRYPSIN

A nonapeptide, H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OH, corresponding to sequence 41-49 of eglin c inhibited leukocyte cathepsin G and alpha-chymotrypsin with K-i values of 2.2 x 10(-5) and 7.2 x 10(-6) M, respectively, although eglin c itself inhibited leukocyte elastase, cathepsin G and alpha-chymotrypsin with K-i values of 6.0 x 10(-9), 5.5 x 10(-9) and 2.5 x 10(-9) M, respectively. The inhibitory activity of the nonapeptide decreased following incubation with cathepsin G due to the cleavage of the Leu(45)-Asp(46) peptide bond. Therefore, Leu(45) and/or Asp(46) were replaced with D-amino acids and the inhibitory activities of the resultant nonapeptides were examined. Their inhibitory activities against cathepsin G and alpha-chymotrypsin were much weaker than those of the all-L-type nonapeptide, suggesting that the amino acids at the active site, Leu(45) and Asp(46) are required to be in the L-configuration for potent activity.