Peptidyl epoxides extended in the P′ direction as cysteine protease inhibitors: Effect on affinity and mechanism of inhibition

N Perlman, M Hazan, M Shokhen, A Albeck

Index: Perlman, Nurit; Hazan, Maya; Shokhen, Michael; Albeck, Amnon Bioorganic and Medicinal Chemistry, 2008 , vol. 16, # 19 p. 9032 - 9039

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Citation Number: 5

Abstract

Endo peptidyl epoxides, in which the central epoxidic moiety replaces the scissile amide bond of a P3–P3′ peptide, were designed as cysteine proteases inhibitors. The additional P′–S′ interactions, relative to those of an exo peptidyl epoxide of the same P3–P1 sequence, significantly improved affinity to the enzymes papain and cathepsin B, but also changed the mode of inhibition from active-site directed inactivation to reversible ...