tailieunhanh - Báo cáo khoa học: A novel dicyclodextrinyl diselenide compound with glutathione peroxidase activity

A 6A,6A¢-dicyclohexylamine-6B,6B¢-diselenide-bis-b-cyclodextrin (6-CySeCD) was designed and synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). In this novel GPX model,b-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. | ễFEBS Journal A novel dicyclodextrinyl diselenide compound with glutathione peroxidase activity Shao-Wu Lv1 Xiao-Guang Wang1 Ying Mu1 Tian-Zhu Zang1 Yue-Tong Ji1 Jun-Qiu Liu2 Jia-Cong Shen2 and Gui-Min Luo1 1 Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education Jilin University Changchun China 2 Key Laboratory for Supramolecular Structure and Materials of the Ministry of Education Jilin University Changchun China Keywords cyclodextrins enzyme mimics glutathione peroxidase selenium substrate binding Correspondence . Luo Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education Jilin University 2519 Jiefang Road Changchun 130021 China Fax 86 431 8898 0440 Tel 86 431 8849 8974 E-mail luogm@ Received 12 February 2007 revised 27 May 2007 accepted 31 May 2007 doi A 6A 6A -dicyclohexylamine-6B 6B -diselenide-bis-b-cyclodextrin 6-CySeCD was designed and synthesized to imitate the antioxidant enzyme glutathione peroxidase GPX . In this novel GPX model b-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 -di-selenide-bis-cyclodextrin 6-SeCD and 2-phenyl-1 2-benzoisoselenazol-3 2H -one Ebselen in the reduction of H2O2 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 .