Synthesis of a trihexacontapeptide corresponding to the sequence 8-70 of eglin c and studies on the relationship between the structure and the inhibitory activity against human leukocyte elastase, cathepsin G and alpha-chymotrypsin.
A trihexacontapeptide corresponding to the sequence 8-70 of eglin c and its related peptides were synthesized by the conventional solution method and their inhibitory activity against human leukocyte elastase, cathepsin G and alpha-chymotrypsin was examined. Although synthetic eglin c (41-49) inhibited cathepsin G and alpha-chymotrypsin (Ki = 4.0 x 10(-5) M and 2.0 x 10(-5) M, respectively) but not leukocyte elastase, the synthetic trihexacontapeptide potently inhibited cathepsin G, alpha-chymotrypsin and leukocyte elastase (Ki = 1.8 x 10(-9) M, 1.4 x 10(-9) M and 2.2 x 10(-9) M, respectively). The relationship between the structure of eglin c and the inhibitory activity against the above enzymes is also described.
Okada
Y
Y
Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Tsuboi
S
S
Tsuda
Y
Y
Nagamatsu
Y
Y
Yamamoto
J
J
D000595:Amino Acid Sequence; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D004563:Electrochemistry; D006801:Humans; D006860:Hydrogen Bonding; D019272:Leukocyte Elastase; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors / Q000737:chemistry*; D015843:Serpins; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C028656:eglin proteinase inhibitors; D002403:Cathepsins; D012697:Serine Endopeptidases; D002918:Chymotrypsin; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase