Journal of medicinal chemistry

Design, Synthesis, Molecular Modeling Studies, and Calpain Inhibitory Activity of Novel α-Ketoamides Incorporating Polar Residues at the P1'-Position

IO Donkor, J Han, X Zheng

Index: Donkor, Isaac O.; Han, Jie; Zheng, Xiaozhang Journal of Medicinal Chemistry, 2004 , vol. 47, # 1 p. 72 - 79

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Citation Number: 24

Abstract

A series of novel α-ketoamides incorporating stereoisomeric residues with different electronic properties at the P1'-position were synthesized to study the electronic requirements for inhibitor binding to the S1'-subsite of calpain I. The results of the study suggested the presence of an acidic amino acid residue at the S1'-subsite of calpain I. For example, ester 1a (Cbz-l-Leu-l-Phe-CO-d-Phe-OMe) was over 450-fold more potent than ...