Nonenzymatic Models

Unlike DDH, 5,6-LAM, and MCM, for which chemical examples of radical isomerizations are available, there is no nonenzymatic model reaction for the isomerization of the 4-glutamyl radical identified as the intermediate observable by EPR spectroscopy at the active site of The accepted mechanism is the radical fragmenta-... 

Several model reactions for the a,P-dehydrogenation of acid anions via the enolate have been worked out (Scheme 2.4.2). Regioselective hydroxylation of the nonactivated P-carbon atom, which is standard in biochemistry, has not been achieved in nonenzymatic model reactions. Heteroatoms (e.g, Br) can only be introduced at the (position with external reagents (Scheme 2.4.2). 

Masuura, T., Matsushima, H. and Nakashima, R. (1970). Photosensitized oxygenation of 3-hydroxyf1avones as an nonenzymatic model for quercetinase. Tetrahedron., 25, 435-443. 

In conclusion, the tautomerization is intramolecular and the suprafacial 1,3 proton shift occurs across a azaallylic anion. The model differs slightly, however, from the biological system by providing competing stereochemical and isotope-labeling reactions pathways. Therefore, coenzymes carry out stereospecific reactions due to their apoenzymes, while nonenzymatic model reactions are not as stereospecific (310). 

To assess the effect of protein binding on catalysis, we compared the initial rates of [1] oxidation by t-butylhydroperoxide in the presence of selenolsubtilisin and diphenyldiselenide, a nonenzymatic model compound. At low substrate concentrations the enzymatic reaction is roughly 70,000 times faster than the selenocystein catalyzed process. Clearly, the redox activity of the selenium group is considerably increased in the active site of subtilisin. Further characterization of the redox chemistry of selenolsubtilisin is in progress. We believe that the information gained in this study will provide a better understanding of how natural glutathione peroxidase works. 

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