CHARACTERIZATION OF A CONTINUOUS FLUOROGENIC ASSAY FOR CALPAIN-I - KINETIC EVALUATION OF PEPTIDE ALDEHYDES, HALOMETHYL KETONES AND (ACYLOXY)METHYL KETONES AS INHIBITORS OF THE ENZYME

被引：33

作者：

HARRIS, AL ^{[1
]}

GREGORY, JS ^{[1
]}

MAYCOCK, AL ^{[1
]}

GRAYBILL, TL ^{[1
]}

OSIFO, IK ^{[1
]}

SCHMIDT, SJ ^{[1
]}

DOLLE, RE ^{[1
]}

机构：

[1] STERLING WINTHROP PHARMACEUT RES DIV,DEPT MED CHEM,COLLEGEVILLE,PA 19426

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 04期

关键词：

D O I：

10.1016/0960-894X(95)00042-R

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Z-Leu-Arg-(7-methoxynaphthyl) amide (1) is a substrate for calpain I. The specificity constant for 1 (k(cat)/K-m = 1405 +/- 40 M(-1) s(-1)) is 10x greater than for any previously reported fluorogenic substrate. Using this substrate, a sensitive, continuous fluorogenic assay was developed permitting the identification of Z-(D)Ala-Leu-Phe-(OCO-2,6-Fl(2)-Ph) (69) as the first selective (>100-fold versus cathepsins B and L) time-dependent inhibitor of the enzyme.

引用

页码：393 / 398

页数：6

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