Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug

被引:39
作者
Erba, F
Fiorucci, L
Pascarella, S
Menegatti, E
Ascenzi, P
Ascoli, F
机构
[1] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy
[2] Univ Rome La Sapienza, Dept Biochem Sci Alessandro Rossi Fanelli, I-00185 Rome, Italy
[3] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy
[4] Univ Rome Tre, Dept Biol, I-00146 Rome, Italy
关键词
human tryptase; bovine tryptase; gabexate mesylate; enzyme inhibition; structural aspects;
D O I
10.1016/S0006-2952(00)00550-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Gabexate mesylate is a non-antigenic synthetic inhibitor of trypsin-like serine proteinases that is therapeutically used in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. Considering the structural similarity between gabexate mesylate and arginine-based inhibitors of trypsin-like serine proteinases. the effect of gabexate mesylate on human and bovine mast cell tryptase action was investigated. Values of the inhibition constant (K-i) for gabexate mesylate binding to human and bovine tryptase were 3.4 x 10(-9) M and 1.8 x 10(-7) M (at pH 7.4 and 37.0 degrees), respectively. Furthermore, gabexate mesylate inhibited the fibrinogenolytic activity of human tryptase. On the basis of the available x-ray crystal structure of human tryptase, the possible binding mode of gabexate mesylate to human and bovine tryptase was analyzed. Human tryptase inhibition by gabexate mesylate may account for the reported prevention of inflammation, erosion, and ulceration of skin and mucosae. (C) 2001 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:271 / 276
页数:6
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