Yanzhen Yin

Smart microgel catalyst with modulatory glutathione peroxidase activity

Glutathione peroxidase (GPx) is a key antioxidant enzyme involved in scavenging of reactive oxygen species and protects cells from oxidative damage. Consequently many efforts have been devoted to develop artificial catalysts with GPx functions. For constructing a smart GPx model, GPx active sites were introduced into temperature responsive poly(N-isopropylacrylamide) (polyNIPAM) scaffolds. By combining the binding ability endowed from micro-pores of functional microgels and the catalytic moiety tellurium, this new microgel catalyst exhibits high GPx-like catalytic activity with typical saturation kinetics behavior as a real catalyst. Compared with diphenyl diselenide (PhSeSePh), a well-studied GPx mimic, it is about 339000-fold more efficient than that of PhSeSePh for catalyzing the reduction of cumene hydroperoxide (CUOOH) by 3-carboxyl-4-nitrobenzenethiol (TNB). More importantly, the catalytic efficiency of this microgel enzyme model displays an obvious temperature responsive characteristic. The catalytic activity of the microgel can be turned on and off reversibly by changing the temperature. At 32 °C it demonstrates the highest GPx-like activity, as the temperature increses up to above 50 °C, the GPx-like activity of the microgel is almost lost. Through detailed studies of catalytic behavior for structurally different substrates, the fluorescence spectra with a pyrene probe combined with the size determined by Zetasizer nano instrument demonstrate that the dramatic efficiency alteration of the microgel catalyst is mainly due to the change of the pore structure in the microgel.

A modulatory bifunctional artificial enzyme with both SOD and GPx activities based on a smart star-shaped pseudo-block copolymer

An artificial smart bifunctional enzyme with both superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was successfully constructed by the self-assembly of a porphyrin core with four suspensory adamantyl moieties and β-cyclodextrin-terminated temperature-sensitive copolymer through host–guest interaction in aqueous solution. The Mn(III) porphyrin, Mn(III)meso-tetra[1-(1-adamantyl methyl ketone)-4-pyridyl] porphyrin (MnTPyP-M-Ad), was designed as both a “supramolecular linker” and an efficient active site of SOD and the temperature-responsive block copolymer (β-CD-PEG-b-PNIPAAm-Te) with incorporated tellurium moieties in the PNIPAAm chain as GPx active sites was synthesized by ATRP. As a new type of artificial bifunctional enzymes, it exhibited stable SOD-like activity of 0.137 μM (IC50) at 37 °C, and high GPx catalytic efficiency with temperature-responsive dependence characteristic, and the new artificial enzyme was found to exhibit the highest GPx catalytic efficiency (v0 = 8.11 μM min−1) in close to physical temperature.

A supramolecular bifunctional artificial enzyme with superoxide dismutase and glutathione peroxidase activities

For constructing a bifunctional antioxidative enzyme with both superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, a supramolecular artificial enzyme was successfully constructed by the self-assembly of the Mn(III)meso-tetra[1-(1-adamantyl methyl ketone)-4-pyridyl] porphyrin (MnTPyP-M-Ad) and cyclodextrin-based telluronic acid (2-CD-TeO(3)H) through host-guest interaction in aqueous solution. The self-assembly of the adamantyl moieties of Mn(III) porphyrin and the beta-CD cavities of 2-CD-TeO(3)H was demonstrated by the NMR spectra. In this supramolecular enzyme model, the Mn(III) porphyrin center acted as an efficient active site of SOD and tellurol moiety endowed GPx activity. The SOD-like activity (IC(50)) of the new catalyst was found to be 0.116 microM and equals to 2.56% of the activity of the native SOD. Besides this, supramolecular enzyme model also showed a high GPx activity, and a remarkable rate enhancement of 27-fold compared to the well-known GPx mimic ebselen was observed. More importantly, the supramolecular artificial enzyme showed good thermal stability.

Incorporation of glutathione peroxidase active site into polymer based on imprinting strategy.

Glutathione peroxidase (GPx, EC 1.11.1.9) is a key enzyme involved in scavenging of reactive oxygen species in biological system. For developing an efficient GPx-like antioxidant, catalytically necessary amino acid derivatives which located near the GPx active center were prepared as functional monomers. Via predetermined imprinting with substrate glutathione (GSH), a polymer-based GPx mimic with a similar structure of catalytic center of natural GPx was developed, and it demonstrated high-catalytic efficiency and substrate specificity. The imprinting polymer (I-PEM) exhibits GPx-like activity about three times higher than that of 2-SeCD, a cyclodextrin-based GPx mimic. The detailed studies on kinetics revealed that not only the substrate binding but also positional arrangement of reacting groups contribute significantly to the catalytic efficiency of the peroxidase model.

Construction of Smart Glutathione Peroxidase Mimic Based on Hydrophilic Block Copolymer with Temperature Responsive Activity

A temperature-sensitive block copolymer (PAAm-b-PNIPAAm-Te) with a glutathione peroxidase-like active site was synthesized via ATRP. As a new glutathione peroxidase (GPx) mimic, it displays typical saturation kinetic behaviors and high catalytic activity. More importantly, the catalytic activity of the polymer can be well modulated by changing the temperature. The experiments proved that a change in the self-assembly structure of the polymer plays a key role for the modulation of catalytic activity. As a contrast, another block copolymer, PAAm-Te-b-PNIPAAm, was synthesized. In comparison with PAAm-b-PNIPAAm-Te, the different temperature dependent catalytic behavior seen further indicates that the micellar structure plays an important role in modulating the catalytic activity of the smart enzyme model.

Construction of a Hyperbranched Supramolecular Polymer as a Bifunctional Antioxidative Enzyme Model

A HBSP has been designed as a novel bifunctional enzyme model with SOD and GPx activity by host/guest-directed self-assembly of MnTPyP-M-Ad and 6-Te-diCD. The structure of the host/guest complex was elucidated by (1) H NMR spectra, and the HBSP was characterized by SEM, DLS and measurement of catalytic properties. In the bifunctional enzyme model, the Mn(III) porphyrins act as efficient SOD active sites and the tellurol moieties endow GPx activity. The SOD-like activity (IC(50) ) of this new supramolecular catalyst was found to be 1.05 × 10(-7) M, which corresponds to 2.82% of the activity of the native SOD enzyme. Besides this, the hyperbranched supramolecular polymer also shows a higher GPx activity (ν(0 ) = 21.7 × 10(-6) M · min(-1) ) than other supramolecular enzyme models.

Construction of an Artificial Glutathione Peroxidase Active Site on Copolymer Vesicles

To construct an efficient GPx mimic, a novel method for preparing polymer-based vesicles carrying GPx-active sites was developed. A 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-PMEO(3) MAs). By altering the molar ratio of the functional copolymers, vesicles with GPx activity were obtained by self-assembly of these functional copolymers through blending. The optimum GPx mimic constructed by the blending process exhibited high catalytic activity and acted as a real catalyst with typical saturation kinetics behavior. The method may be of benefit for designing other enzyme mimics and may cast a light on constructing other biologically related functional nanoparticles.

Construction of a smart glutathione peroxidase mimic with temperature responsive activity based on block copolymer

To construct a smart artificial antioxidative enzyme on a nano-scaffold, a novel method for designing glutathione peroxidase (GPx) active sites on block copolymer vesicles was developed by simple blending predesigned temperature-sensitive block copolymers with the main catalytic units of GPx. A series of functional block copolymers, poly(N-isopropylacrylamide)-b-polyacrylamides loaded with recognition and catalytic sites, were synthesized viaATRP and click chemistry. Through altering the molar ratio of the functional copolymers, the optimum GPx mimic based on copolymer vesicles was obtained by self-assembly of temperature-sensitive block copolymers through a blending process. Significantly, the catalytic activity of the optimum GPx mimic can be well modulated by changing the temperature. It was proved that the change in self-assembly structure of the block copolymer played an important role in the modulation of the catalytic activity. This method not only bodes well for designing smart antioxidative enzyme mimics that could be used in cosmetics as antioxidative additives but also highlights the construction of other regulatory biologically related functional biomaterials.

Design of Artificial Selenoenzymes Based on Macromolecular Scaffolds

The selenoenzyme glutathione peroxidase has received increased attention as one of the antioxidative enzymes exerting important biological roles in living bodies. Over the past decades, much effort has been invested to mimic its catalytic behavior for understanding enzymatic catalytic mechanisms and also for developing potential medicines. A great number of artificial GPxs, ranging from small molecular compounds to macromolecular ones, have been designed and prepared by combining the concept of recognition and catalysis using chemical, biological and supramolecular strategies. In this article, we specify the development of artificial GPxs based on macromolecules as scaffolds, and discuss the power of reduced models in studying the bio-catalytic nature of selenoenzymes.