具有谷胱甘肽过氧化物酶活力的含碲环糊精衍生物

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

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.

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 se- lenium as active atom, aniline group was incorporated into cyclodextrin in proximity to catalyiic tellurium for increasing the stability of nucleophilic intermediate tellurolate, and fl-cyclodextrin（/^-CD） provided a hydro- phobic 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 MTF 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） served in steady-state kinetics studies. Moreover, the novel As native GPx, a ping-pong mechanism was ob- 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.