氮杂肽环氧化物：一类对CD家族半胱氨酸蛋白酶具有选择性的新型抑制剂。

Aza-peptide epoxides: a new class of inhibitors selective for clan CD cysteine proteases.

作者信息

Asgian Juliana L, James Karen Ellis, Li Zhao Zhao, Carter Wendy, Barrett Alan J, Mikolajczyk Jowita, Salvesen Guy S, Powers James C

机构信息

School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta 30332-0400, USA.

出版信息

J Med Chem. 2002 Nov 7;45(23):4958-60. doi: 10.1021/jm025581c.

DOI:10.1021/jm025581c

PMID:12408706

Abstract

Aza-peptide epoxides, a new class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. The inhibitors have second-order rate constants up to 10(5) M(-1) s(-1), with the most potent epoxides having the S,S stereochemistry. The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition with other proteases such as chymotrypsin, papain, or cathepsin B.

摘要

氮杂肽环氧化物是一类新型的不可逆蛋白酶抑制剂，对CD家族半胱氨酸蛋白酶具有特异性。这些抑制剂的二级速率常数高达10⁵ M⁻¹ s⁻¹，最有效的环氧化物具有S,S立体化学结构。氮杂天冬酰胺衍生物是有效的天冬酰胺酶抑制剂，而氮杂天冬氨酸环氧化物对胱天蛋白酶具有特异性。这些抑制剂对其他蛋白酶如胰凝乳蛋白酶、木瓜蛋白酶或组织蛋白酶B几乎没有抑制作用。