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

Authors
HARRIS AL GREGORY JS MAYCOCK AL GRAYBILL TL OSIFO IK SCHMIDT SJ DOLLE RE
Citation
Al. Harris et al., 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, Bioorganic & medicinal chemistry letters, 5(4), 1995, pp. 393-398
Citations number
19
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
5
Issue
4
Year of publication
1995
Pages
393 - 398
Database
ISI
SICI code
0960-894X(1995)5:4<393:COACFA>2.0.ZU;2-B
Abstract
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 d eveloped 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.