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 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 Ki 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 Ki 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 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 alpha-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.
Fujii
A
A
Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Tsuboi
S
S
Asada
K
K
Nagamatsu
Y
Y
Yamamoto
J
J
Okada
Y
Y
D000595:Amino Acid Sequence; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins; D012697:Serine Endopeptidases; D015843:Serpins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D009842:Oligopeptides; D011506:Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D002403:Cathepsins; D012697:Serine Endopeptidases; D002918:Chymotrypsin; C534094:CTSG protein, human; D056649:Cathepsin G