| As an important selenium-containing enzyme, glutathione peroxidase (GPx EC.1.11.1.9) is indispensable for human, which with the basic catalytic characteristic allows the enzymes to adopt diversified biological roles ranging from defence against peroxide damage, redox regulation of metabolic processes, cellular differentiation and apoptosis. So researchers ranging from biologists to chemists have been extensively investigated this important selenium-containing enzyme as it plays the numerous and fundamental roles. Up to now, eight distinct GPxs have been identified in mammals, five of them being selenoproteins in man. Usually, GPx functions to catalyze the reduction of hydroperoxides using glutathione as a specific reducing substrate and plays a major role in the organismal antioxidant defense mechanism protecting cells from oxidative stress, such as such as reperfusion injury, brain ischemia. tumor, cataract, inflammation, and physiological aging. Due to its biologically crucial role, considerable efforts have been devoted to producing organoselenium or tellurium compounds that mimic the properties of GPx in recent years.Recently, in our group, for promoting the catalytic efficiency of the artificial GPx models, more exact imitation of the active site of GPx with the concept of synergy of the recognition and catalysis was carried out based on the understanding of the structure of GPx. Thus, a series of host molecules with high substrate specificity and appropriate catalytic selenium moieties were developed. Afterwards, a genetic engineering strategy was further emplyed to construct well-defined artificial GPx models and a series of telluro-proteins as artificial GPx models with higher catalytic activity were continuously reported. Recently, molecularly imprinted artificial GPx models were developed in view of transition state recognition or mimicking the active site microenvironment of enzymes. Furthermore, various smart nanoenzyme models with controlled catalytic activity were well demonstrated by the combination of biological, supramolecular and nanoscientific strategies. Up to now, some of these artificial GPx models show satisfying enzymatic properties, excitingly, some of them display extraordinarily high activities rivalling native ones.Although artificial GPx models constructed by chemical and genetic strategies previously have demonstrated high catalytic activity, some disadvantages still remain in such efficient GPx models. On the one hand, catalytic factors are commonly combined into one scaffold through covalent chemical methods, which have the limitation of complicated synthetic routes, expensive cost and low productivity. On the other hand, it is difficult to construct the optimum artificial GPx models via altering the molar ratio of the catalytic factors as it is a fixed value. Thus. the construction of artificial GPx models using a simple and efficient method is still a great challenge. Additionally, the construction of a desirable artificial GPx models with smart characteristics of its catalytic efficiency could be regulated by some environmental stimuli is always an interesting job. And how to combine the catalytic factors into one smart artificial GPx models is also a great challenge. Futhermore. could all the challenge mentioned above be resolved in a more simple method using the protocol of supramolecular science? All of them are the challenge we will meet.Recently. ATRP and Click chemistry have flourishing developed, which is one of the significant protocols employed to design versatile functional materials and polymers with complex architectures and compositions. Significantly, a blending process is efficient method to obtain new polymer materials with superior properties compared to those of individual components. Meanwhile, the flourishing development in nano and supramolecular science brings a new field in the design of artificial enzyme. Based on the understanding of the sturcture of GPx and the advantage of ATRP, Click chemistry, blending process, nano and supramolecular science, we have designed three artificial GPx models to meet the challenges mentioned above.1 Construction of artificial GPx based on assembly of block copolymersA series of block copolymers loaded with recognition and catalytic sites were synthesized based on polystyrene-block-poly[tri(ethylene glycol) methyl ether acrylate]s (PS-PMEO3MAs) via Atom Transfer Radical Polymerization and Click chemistry. A simply and efficient artificial GPx models was obtained using the blending process for the first time. A study of the assembly behavior of the blended artificial GPx models and the individual copolymers indicated that the blended artificial GPx models can assemble into uniform and stable vesicles that are analogous to the individual copolymers. which makes the blending process a feasible and excellent method to construct blended artificial GPx models. In particular, the optimum artificial GPx models was achieved through optimizing the structure of the functional block copolymers and changing the molar ratio of three functional block copolymers. PP-Te1, PP-CD2 and PP-q2. Although the specific substrate binding plays an important role in designing a desirable GPx mimic, the match degree among the catalytic factors also makes a great contribution to obtaining high GPx activity. As a new artificial GPx models, considering its high catalytic activity, simple preparation process and better match of catalytic factors, the blended artificial GPx models may make the preparation of efficient artificial GPx models more eassy.2 Construction of smart artificial GPx based on block copolymersPrevious works have well demonstrated that blended process is a simple and efficient protocol to construct blended artificial GPx models. Herein, this simple method was successfully emolyed to construct smart artificial GPx models. As the functional block copolymers loaded with recognition and catalytic sites. PPAM. PPAM-Te, PPAM-N, PPAM-CD were synthesized via ATRP and Click chemistry. Using the blending process, the optimum artificial GPx models (PPAM-N-CD-Temax) was obtained by the self-assembly of temperature-sensitive block copolymers through altering the molar ratio of the functional copolymers. By exploring the catalytic behavior, it is noted that not only the specific substrate binding ability but also the better match among the catalytic factors play an important role in designing a desirable artificial GPx models. Significantly, as a smart blended artificial GPx models. the catalytic activity of the optimum artificial GPx models can be well modulated by changing the temperature. It was proved that a change in the self-assembly structure of the block copolymers at different temperatures plays an important role in the modulation of catalytic activity.3 Construction of smart artificial GPx via supramolecular self-assemblyConsidering that the constructing of smart blended artificial GPx models is successful. an attempt of preparation a more simplified smart blended artificial GPx model via supramolecular chemistry is finished. Herein, the host-polymer CD-PNIPAM was synthesized via ATRP and Click chemistry. And the guest-molecules loaded with catalytic and recognition sites,8 and 9 were synthesized. Subsequently, functional copolymers loaded with recognition and catalytic sites. CD-PNIPAM, Arg-CD-PNIPAM, Te-CD-PNIPAM were obtained via self-assemble between the host-polymer and the guest-molecules. The optimum artificial GPx models was constructed by blending process of three functional copolymers by altering the the molar ratio of them. By exploring the catalytic behavior, this smart blended artificial GPx models constructed via host-guest self-assemble method acted as an real enzyme catalyst. And the catalytic activity of the optimum artificial GPx models can be well modulated by changing the temperature. Considering that such smart artificial GPx models were constructed throuth a simplified protocol, we anticipate that this study will open up a new field in designing a smart antioxidative artificial enzyme. |
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