DESIGN OF A NEW SELECTIVE CYSTEINE PROTEASE INACTIVATOR AND ITS MECHANISTIC IMPLICATIONS

Authors
ALBECK A PERSKY R KLIPER S
Citation
A. Albeck et al., DESIGN OF A NEW SELECTIVE CYSTEINE PROTEASE INACTIVATOR AND ITS MECHANISTIC IMPLICATIONS, Bioorganic & medicinal chemistry letters, 5(16), 1995, pp. 1767-1772
Citations number
32
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
5
Issue
16
Year of publication
1995
Pages
1767 - 1772
Database
ISI
SICI code
0960-894X(1995)5:16<1767:DOANSC>2.0.ZU;2-D
Abstract
Cbz-Phe-epoxide was designed as a selective inactivator of cysteine pr oteases. It exhibits a time- and concentration-dependent inactivation of cysteine proteases, while showing no activity towards serine protea ses. The inhibition is irreversible, correlated with loss of the free active-site thiol, and its rate is at least 10(4) faster than the rate of a model reaction in solution. These results support the proposed a ctive-site directed, protonation-dependent, mechanism-based mode of in activation of cysteine proteases by the new inhibitor.