Study On Synthetisis And Determination Of Eight Kinds Of GPx Mimics

Glutathione peroxidase as an important peroxidase enzymes, is one of the key enzymes remove H₂O₂ and other hydroperoxide in order to maintain the reactive oxygen species（ROS） metabolic balance in vivo. ROS imbalance can cause a variety of diseases, including cardiovascular disease, Alzheimer’s psychosis. Thus, the antioxidant enzyme GPx has high medicinal potential. Known natural GPx has many defects, such as instability in vitro, and poor availability that limits the development and utilization of natural GPx.The catalytic functional groups of natural GPx is selenium（Sec）, selenium in the enzymatic degradation of hydroperoxide has played a very important role characteristics. Introducing selenium in many small molecules or more active elements tellurium synthesized GPx mimic enzyme has become one of the hot artificial enzyme research. Introducing selenium or tellurium in many small molecules to synthesized GPx mimic enzyme has become one of the hot artificial enzyme resea.According to a known class of cyclodextrin GPx mimetic enzyme structure, including 2,2’-Seleno-（2-deoxy-β-cyclodextrin）（2-SeCD）, 6,6’-Seleno-（6-deoxy-β-cyclodextrin）（6-SeCD）, 2,2′-Ditellurobis-（2-deoxy-β-cyclodextrin）（2-TeCD）, 6,6′-Ditellurobis-（6-deoxy-β-cyclodextrin）（6-TeCD） and 6,6′-Telluro-bis（6-deoxy-β-cyclodextrin）（6-TediCD）, we designed and synthesized similarly three cyclodextrin derivatives, including 2,2′-Seleno-bis（2-deoxy-β-cyclodextrin）（2-SediCD）, 6,6′-Seleno-bis（6-deoxy-β-cyclodextrin）（6-SediCD） and 2,2′-Telluro-bis（2-deoxy-β-cyclodextrin）（2-TediCD）. We use two GPx enzyme activity assay method to determine the enzyme activity of the enzyme simulate, the results show that eight kinds of simulation have certain enzymes GPx enzyme activity associated with vitality and with the same reported in the literature. Wherein the 2-TeCD has the maximum activity（dual enzyme activity was measured by coupling 46.7U / μM, directly measured by enzyme activity was 1155 U / μM）, and the 6-TediCD has the least activity（dual enzyme activity was measured by coupling 0.1U / μM, directly measured by enzyme activity was 90 U / μM）. These eight GPx mimic enzymes have the similar structure, but quite different vitality, 2-TeCD many times the 6-SediCD（more than 400 times the difference between double enzyme activity, vitality direct method more than 10 times）. The reason mimic enzymes showed a greater vitality different analysis by steady-state kinetics method. the data show that the cyclodextrin telluride substrate material with thiol（RSH） is higher than a similar rate constant（kb） selenide cyclodextrin, The 2-position mifed cyclodextrin and hydrogen peroxide（H₂O₂） similar rate constant（ka） value higher than the 6-position mifed cyclodextrins. The dual-bridging cyclodextrin single bridge cyclodextrin has higher ka and kb value than bis-bridging cyclodextrin. Combination of these factors, these eight mimics activity showed:（1） Tellurium mimics have higher activity than selenium mimics;（2） Dual-bridging mimics have higher activity than bis-bridging mimics;（3） 2-position mifed cyclodextrin have higher activity than 6-position mifed cyclodextrin.