Enzyme mimics synthetic polymers

The wide variety of enzymes available gives for promise enzymatic derivatization to become a potent analytical tool in the future. Better understanding and theoretical formulations will lead to commercial availability of immobilized enzymes and consequently to more ready use of them. Since in such systems a low content of organic cosolvent in the mobile phase can only be tolerated (whereas a compromise has to be made as far as the optimum mobile phase pH is concerned), artificial enzymes, which are synthetic polymer chains having functional groups that mimic the biocatalytic activity of natural enzymes, are currently being synthesized and investigated as a means to overcome such limitations (276). 

Molecular imprinting in synthetic polymers was reported for the first time in 1972 [1--4]. The initial idea was to obtain in the polymer highly specific binding clefts with a predetermined size, shape and three-dimensional arrangement of functional groups. Later on, further experiments demonstrated that such functionalised cavities could be tailored to mimic the active sites of enzymes ( enzyme analogue built polymer ). 

Electrocatalytic groups such as porphyrins and phthalocyanines that act as supramolecular hosts for different metals and mimic the active sites of various proteins are commonly used in amperometric sensors [66,67]. A biomimetic sensor based on an artificial enzyme or synzyme has been demonstrated [68]. The artificial enzyme used in this study was a synthetic polymer (quaternised polyethyleneimine containing 10% primary amines) which decarboxylated oxaloacetate. The product carbon dioxide was detected potentiometrically via a gas membrane electrode. 

Synzymes are synthetic polymers with catalytic activity mimicing that of enzymes. Numerous investigations in search of synzymes have been reported " The main approach for the design of mzyn shas been to modify polymers and mold their conformation to maricedly increase their affinity for small molecules. 

The possibility to tailor-make MIPs towards a desired selectivity in combination with the high stability of the materials under a broad range of conditions has rendered MIPs attractive for the development of synthetic enzymes [243, 244]. A popular strategy has been to imprint a transition state analog to obtain a polymer that reduces the activation energy of the reaction. Catalytically active groups are often included in the polymer network. This approach has been applied towards ester and amide hydrolysis reactions [245, 246]. Examples of other reactions where MIPs have been utilized as enzyme mimics are isomerization [247], transamination [248], Diels-Alder reaction [249], 3-elimination [250] and regioselective cycloaddition [251]. 

Molecular imprinting recent innovations in synthetic polymer receptor and enzyme mimics... 

In addition to chemical hydrolysis, hydrolysis by enzymes can operate as an alternative degradation process. It has become widely accepted that biodegradable synthetic polymers tend to be designed to mimic those structures prevailing in nature, since enzymes produced by microbial populations may not discriminate between polymers of similar structure.11 Synthetic nonpolypeptidic, chiral polyamides could mimic natural peptides or proteins, resulting in biodegradable products useful in biomedicine. 

Nolte et al 46) produced an artificial enzyme based on the T4 replisome and applied it to the epoxidation of double bonds in synthetic polymers. Smith et al 51) reported that horseradish peroxidase catalyzes the oxidative polymerization of glucuronic acid. In recent literature, many biomimetic macromolecules with enzyme-like structures or functions have been reported including those that are dendrimers 64-66), those that have specified three-dimensional structures or recognition elements created by molecular imprinting 67), and other enzyme mimics 68). 

The PAOM resins were designed to mimic antithrombin III affinity for thrombin by partially substituting, on the backbone of the synthetic polymer, one of the major binding sites of the inhibitor, namely L-arginyl methyl ester. This strategy would be justified if a real involvement of the active seryl residue of thrombin were found in the enzyme-PAOM interactions and not in the enzyme-PSSO interactions. 

As regard to enzyme mimics formed with totally synthetic polymers, relatively simple water-soluble polymers with catalytic functionalities were employed in the early work before 1980.Although simulation of enzymatic behavior was successful to a certain extent by employing such prototype models, recent interests focused on more intelligent synthetic polymers, such as imprinted polymers and dendrimers. " ... 

Other milestones are grafting by radical, cationic, anionic and coordinative polymerization use of semisynthetic and synthetic polymers as ion exchange resins " and catalysts which, in some cases, mimic and even surpass the efficiency of enzymes and solid phase peptide synthesis by Merrifield and Letsinger. ... 

The results of these studies and others reported previously demonstrate that the 1-oxypyridinyl group is an effective catalyst for the transacylation reactions of derivatives of carboxylic and phosphoric acids when incorporated in small molecules and polymers. Furthermore, this catalytic site exhibits high selectivity for acid chlorides in the presence of acid anhydrides, amides, and esters. Therefore, catalysts bearing this group as the catalytic site can be used successfully in synthetic applications that require such specificity. The results of this work suggest that functionalized polysiloxanes should be excellent candidates as catalysts for a wide variety of chemical reactions, because they combine the unique collection of chemical, physical, and dynamic-mechanical properties of siloxanes with the chemical properties of the functional group. Finally, functionalized siloxanes appear to mimic effectively enzyme-lipophilic substrate associations that contribute to the widely acknowledged selectivity and efficiency observed in enzymic catalysis. 

Parton et al. [126] reported on the development of a synthetic system that mimics the cytochrome P-450 enzyme. They embedded zeolite Y crystallites containing encapsulated iron phthalocyanine complexes in a polymer membrane. Using tertiary-butylhydroperoxide as oxidant, this catalytic system oxidizes alkanes at room temperature with rates comparable to those of the real enzyme. 

The thermal polymers are incapable of mimicing a peptide or protein to the exact extent that the product of a stepwise synthesis does. An exact duplication of a functional protein, however, does little to elucidate the reason for its activity modification and study of the effect on activity are necessary. Systematic synthetic modification of polymeric models is easily achieved in the case of thermal polyamino acids. They are prepared with much ease and in large numbers, and their quantitative compositions can be regulated and controlled simply. Examples are already at hand to illustrate the use of the thermal method to evaluate qualitatively the kinds of amino acid residue that are necessary for, contributory to, or detrimental to, activity. Such studies augment information from enzymes and from nonthermal models. 

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