基于statine的抑制剂对多种人天冬氨酸蛋白酶的选择性。
The selectivity of statine-based inhibitors against various human aspartic proteinases.
作者信息
Jupp R A, Dunn B M, Jacobs J W, Vlasuk G, Arcuri K E, Veber D F, Perlow D S, Payne L S, Boger J, de Laszlo S
机构信息
Department of Biochemistry, University of Wales College of Cardiff, U.K.
出版信息
Biochem J. 1990 Feb 1;265(3):871-8. doi: 10.1042/bj2650871.
Abstract
The interactions of five human enzymes (renin, pepsin, gastricsin, cathepsin D and cathepsin E) and the aspartic proteinase from Endothia parasitica with several series of synthetic inhibitors were examined. All of the inhibitors contained the dipeptide analogue statine or its phenylalanine or cyclohexylalanine homologues in the P1-P1' positions. The residues occupying the peripheral sub-sites (P4 to P3') were varied systematically and inhibitory constants were determined for the interactions with each of the proteinases. Inhibitors were elucidated that specifically inhibited human renin and did not affect any of the other human enzymes or the fungal proteinase. With suitable selection of residues to occupy individual sub-sites, effective inhibitors of specific human aspartic proteinases may now be designed.
摘要
研究了五种人类酶（肾素、胃蛋白酶、胃泌酶、组织蛋白酶D和组织蛋白酶E）以及寄生内座壳天冬氨酸蛋白酶与几系列合成抑制剂的相互作用。所有抑制剂在P1-P1'位置均含有二肽类似物司他汀或其苯丙氨酸或环己基丙氨酸同系物。系统地改变占据外周亚位点（P4至P3'）的残基，并测定与每种蛋白酶相互作用的抑制常数。已阐明了特异性抑制人类肾素且不影响任何其他人类酶或真菌蛋白酶的抑制剂。通过适当选择占据各个亚位点的残基，现在可以设计出特异性人类天冬氨酸蛋白酶的有效抑制剂。
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