Amino Acids and Peptides. XXXVII. Synthesis of Stereoisomeric Nonapeptides Corresponding to Sequence 41-49 of Eglin c and Examination of Their Inhibitory Activity against Human Leukocyte Cathepsin G and α-Chymotrypsin

Abstract

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 α-chymotrypsin with K_i values of 2.2×10^-5 and 7.2×10^-6M, respectively, although eglin c itself inhibited leukocyte elastase, cathepsin G and α-chymotrypsin with K_i values of 6.0×10^-9, 5.5×10^-9 and 2.5×10^-9M, respectively. The inhibitory activity of the nonapeptide decreased following incubation with cathepsin G due to the cleavage of the Leu⁴⁵-Asp⁴⁶ peptide bond. Therefore, Leu⁴⁵ and/or Asp⁴⁶ were replaced with D-amino acids and the inhibitory activities of the resultant nonapeptides were examined. Their inhibitory activities against cathepsin G and α-chymotrypsin were much weaker than those of the all-L-type nonapeptide, suggesting that the amino acids at the active site, Leu⁴⁵ and Asp⁴⁶ are required to be in the L-configuration for potent activity.