A novel dicyclodextrinyl diselenide compound with glutathione peroxidase activity

作者：Lv Shao Wu; Wang Xiao Guang; Mu Ying; Zang Tian Zhu; Ji Yue Tong; Liu Jun Qiu; Shen Jia Cong; Luo Gui Min^*

来源：FEBS Journal, 2007, 274(15): 3846-3854.

DOI：10.1111/j.1742-4658.2007.05913.x

• cyclodextrins
• enzyme mimics
• glutathione peroxidase
• selenium
• substrate binding

A 6A,6A'-dicyclohexylamine-6B,6B'-diselenide-bis-p-cyclodextrin (6-CySeCD) was designed and synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). In this novel GPX model, P-cyclodextrin provided a hydrophobic environment for substrate binding within its cavity, and a cyclohexylamine group was incorporated into cyclodextrin in proximity to the catalytic selenium in order to increase the stability of the nucleophilic intermediate selenolate. 6-CySeCD exhibits better GPX activity than 6,6'-diselenide-bis-cyclodextrin (6-SeCD) and 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (Ebselen) in the reduction of H2O1, tert-butyl hydroperoxide and cumenyl hydroperoxide by glutathione, respectively. A ping-pong mechanism was observed in steady-state kinetic studies on 6-CySeCD-catalyzed reactions. The enzymatic properties showed that there are two major factors for improving the catalytic efficiency of GPX mimics. First, the substrate-binding site should match the size and shape of the substrate and second, incorporation of an imido-group increases the stability of selenolate in the catalytic cycle. More efficient antioxidant ability compared with 6-SeCD and Ebselen was also seen in the ferrous sulfate/ascorbate-induced mitochondria damage system, and this implies its prospective therapeutic application.

• 出版日期2007-8
• 单位吉林大学