Characterization of alpha-nitromethyl ketone as a new zinc-binding group based on structural analysis of its complex
Shou-Feng Wang1, Guan Rong Tian, Wen-Zheng Zhang
1Key Laboratory of Biological Resources and Functional Molecules of the Changbai Mountains, Ministry of Education, Yanbian University, Yanji, Jilin, China.
Abstract:
Zinc-binding groups (ZBGs) are exhaustively applied in the development of the new inhibitors against a wide variety of physiologically and pathologically important zinc proteases. Here the alpha-nitro ketone was presented as a new ZBG, which is a transition-state analog featured by the unique bifurcated hydrogen bonds at the active site of carboxypeptidase A based on the structural analysis. Introduction of a nitro group at the alpha-position of the ketone could provide more non-covalent interactions without loss of the abilities to form a tetrahedral transition-state analog.
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