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

• Published in: Chemical & pharmaceutical bulletin Vol. 42; no. 7; pp. 1518 - 1521
• Main Authors: FUJII, Ayumi, TSUBOI, Satoshi, ASADA, Keiichi, NAGAMATSU, Yoko, YAMAMOTO, Junichiro, OKADA, Yoshio
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1994; Maruzen
• Subjects: Amino Acid Sequence; analog; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Cathepsin G; Cathepsins - antagonists & inhibitors; chemical synthesis; Chymotrypsin - antagonists & inhibitors; eglin c (41-49); Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Hydrolases; leukocyte cathepsin G; Leukocytes - enzymology; Molecular Sequence Data; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacology; Proteins; Serine Endopeptidases; Serpins - chemical synthesis; Serpins - chemistry; Serpins - pharmacology; Stereoisomerism; structure-activity relationship; α-chymotrypsin; Human; Leukocyte elastase; D stereoisomer; Serine endopeptidases; Peptides; Enzyme; Cathepsin G; Enzyme inhibitor; Nonapeptide; Liquid phase; In vitro; Chymotrypsin; Structure activity relation; Peptide fragment; Hydrolases; Peptide synthesis; Proteinases
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.42.1518

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 Ki 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 Ki 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.