Premium
A novel dicyclodextrinyl diselenide compound with glutathione peroxidase activity
Author(s) -
Lv ShaoWu,
Wang XiaoGuang,
Mu Ying,
Zang TianZhu,
Ji YueTong,
Liu JunQiu,
Shen JiaCong,
Luo GuiMin
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05913.x
Subject(s) - diselenide , diphenyl diselenide , glutathione peroxidase , peroxidase , chemistry , glutathione , biochemistry , enzyme , organic chemistry , selenium
A 6A,6A′‐dicyclohexylamine‐6B,6B′‐diselenide‐bis‐β‐cyclodextrin (6‐CySeCD) was designed and synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). In this novel GPX model, β‐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 H 2 O 2 , 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.