用于区分半胱氨酸蛋白酶钙蛋白酶II、组织蛋白酶L和组织蛋白酶B的肽基重氮甲烷抑制剂的设计。
The design of peptidyldiazomethane inhibitors to distinguish between the cysteine proteinases calpain II, cathepsin L and cathepsin B.
作者信息
Crawford C, Mason R W, Wikstrom P, Shaw E
机构信息
Department of Biochemistry, Strangeways Laboratory, Cambridge, U.K.
出版信息
Biochem J. 1988 Aug 1;253(3):751-8. doi: 10.1042/bj2530751.
Abstract
A series of peptidyldiazomethanes was synthesized and tested as inactivators of the cysteine proteinases calpain II, cathepsin L and cathepsin B. Inactivators that react rapidly and that show a degree of selectivity between the enzymes were identified. Z-Tyr(I)-Ala-CHN2 (where Z represents benzyloxycarbonyl) reacts rapidly with cathepsin L and more slowly with cathepsin B, but does not inhibit calpain II. Z-Leu-Leu-Tyr-CHN2 reacts rapidly with cathepsin L and calpain II but very slowly with cathepsin B. Boc-Val-Lys(epsilon-Z)Leu-Tyr-CHN2 (where Boc represents t-butyloxycarbonyl) reacts more rapidly with calpain II than with cathepsin L or cathepsin B. The discriminating inhibitory effects of these compounds make them potentially useful for investigation of enzyme functions in vivo. The data presented also provide insights into the subsite specificity of calpain.
摘要
合成了一系列肽基重氮甲烷，并将其作为半胱氨酸蛋白酶钙蛋白酶II、组织蛋白酶L和组织蛋白酶B的失活剂进行测试。鉴定出了能快速反应且在这些酶之间表现出一定选择性的失活剂。Z-Tyr(I)-Ala-CHN2（其中Z代表苄氧羰基）与组织蛋白酶L反应迅速，与组织蛋白酶B反应较慢，但不抑制钙蛋白酶II。Z-Leu-Leu-Tyr-CHN2与组织蛋白酶L和钙蛋白酶II反应迅速，但与组织蛋白酶B反应非常缓慢。Boc-Val-Lys(ε-Z)Leu-Tyr-CHN2（其中Boc代表叔丁氧羰基）与钙蛋白酶II的反应比与组织蛋白酶L或组织蛋白酶B的反应更快。这些化合物具有的区分性抑制作用使其有可能用于体内酶功能的研究。所呈现的数据也为钙蛋白酶的亚位点特异性提供了见解。
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