高等学校化学学报 ›› 2013, Vol. 34 ›› Issue (9): 2146.doi: 10.7503/cjcu20121130

• 有机化学 • 上一篇    下一篇

具有谷胱甘肽过氧化物酶活力的含碲环糊精衍生物

吕冰聪1, 董森1, 薛峤2, 宗慧1, 吕绍武1, 罗贵民1   

  1. 1. 吉林大学分子酶学工程教育部重点实验室, 长春 130012;
    2. 吉林大学理论化学计算国家重点实验室, 长春 130023
  • 收稿日期:2012-12-14 出版日期:2013-09-10 发布日期:2013-08-30
  • 作者简介:吕绍武,男,博士,副教授,主要从事模拟酶研究.E-mail:lvsw@jlu.edu.cn
  • 基金资助:

    国家自然科学基金(批准号:21002040);吉林大学科学前沿与交叉学科创新项目(批准号:200903093,2010ME005)资助.

New Derivative of Tellurium Containing Cyclodextrin(6-AnSeCD) with Glutathione Peroxidase(GPx) Activity

LÜ Bing-Cong1, DONG Seng1, XUE Qiao2, ZONG Hui1, LÜ Shao-Wu1, LUO Gui-Min1   

  1. 1. Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130012, China;
    2. State Key Lab of Theoretical and Computational Chemistry, Jilin University, Changchun 130023, China
  • Received:2012-12-14 Online:2013-09-10 Published:2013-08-30

摘要:

设计并合成了谷胱甘肽过氧化物酶(GPx)模拟物6A,6A'-二苯胺-6B,6B'-二碲桥联-β-环糊精(6-AnTeCD), 采用双酶偶联法进行GPx活力测定和酶反应动力学分析, 通过噻唑蓝(MTT)比色法评价了6-AnTeCD对H2O2诱导心肌细胞氧化损伤的保护作用. 结果表明, 6-AnTeCD催化谷胱甘肽(GSH)还原过氧化氢(H2O2)的活力高于6-AnSeCD、6,6'-二碲桥联-β-环糊精(6-TeCD)和Ebselen等GPx模拟物. 稳态动力学分析显示, 6-AnTeCD的催化机制为乒乓机制. 6-AnTeCD分子兼具引入底物结合部位和改造催化部位的双重优点, 具有分子量小、毒性低及可有效保护心肌细胞免受氧化损伤的优点.

关键词: 谷胱甘肽过氧化物酶模拟物, 底物结合, 催化部位改造, 含碲环糊精

Abstract:

Because the natural glutathione peroxidase(GPx) has some shortcomings such as instability, antigenicity and poor availability, scientists have paid much attention to its artificial imitation. In the present study, 6A,6A'-dianilino-6B,6B'-ditelluro-bis-β-cyclodextrin(6-AnTeCD) was designed and synthesized to imitate the antioxidant enzyme glutathione peroxidase(GPx). In this novel GPx model, tellurium replaced selenium as active atom, aniline group was incorporated into cyclodextrin in proximity to catalytic tellurium for increasing the stability of nucleophilic intermediate tellurolate, and β-cyclodextrin(β-CD) provided a hydrophobic environment for binding substrate in its cavity. The GPx activities and the kinetics of the mimics were assessed in classical coupled reductase assay. The antioxidant effect of the 6-AnTeCD was evaluated based on MTT assay. The results showed that 6-AnTeCD exhibits better GPx activity than those of 6-AnSeCD, 6-TeCD and Ebselen in the reduction of H2O2 by glutathione(GSH). As native GPx, a ping-pong mechanism was observed in steady-state kinetics studies. Moreover, the novel GPx mimic occupied merits of small molecular weight and low toxicity. Especially, the 6-AnTeCD was found that it could protect cardiac muscle cells from the injury induced by H2O2. These data demonstrated that and 6-AnTeCD has excellent potential in treatment of H2O2-mediated diseases.

Key words: Glutathione peroxidase, Substrate-binding, Catalytic site modification, Tellurium containing cyclodextrin

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