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

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 H_2O_2 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 H_2O_2.These data demonstrated that and 6-AnTeCD has excellent potential in treatment of H_2O_2-mediated diseases.