Enzyme mimicking models

The most promising direction for enzyme modeling is to synthetically mimick the nature of the binding site and the active site in terms of the close similarity of catalytic groups, stereochemistry, interatomic distances and the mechanism of the action of the enzyme. Mimicking of the proton-transfer relay proposed for the mechanism of the action of chymotrypsin is a brilliant example of such work (D Souza and Bender, 1987 and references therein). The miniature organic model of chymotrypsin built on the basis of cyclodextrin and the mechanism of hydrolysis m-tert-butylphenyl acetate is presented in Fig. 6.9. 

Calixarenes similarly to natural detergents easily embed the micelles and bilayers formed by other amphiphiles [54] and can exhibit highly selective catalytic activity as enzyme-mimicking systems. Thus, water-soluble calix[6]arenes 8-11 catalyzed the hydration of 1,4-dihydronicotinamide derivatives, important model compound used to study the properties of the reduced form of the coenzyme nicotinamide adenine dinucleotide (NADH) (Scheme 4.8) [55], The reaction proceeded according to the Michaelis-Menten kinetics. 

Chapter 16), the carbonyl oxygen of the amide substrate is coordinated to the Zn2+ of the enzyme (Figure 2.7). The coordination polarizes the amide to nucleophilic attack and strongly stabilizes the tetrahedral intermediate (equation 2.27). This type of complex formation has been mimicked in model compounds... 

Not just the enzyme but also whole enzyme catalytic systems can be mimicked as an example, if the influence of interaction of an enzyme with its environment is the target of the investigation, frequently either model membrane surfaces or aggregates formed with surfactant molecules such as micelles or vesicles are employed. 

A different redox system model - the model for NADH - was also described by our group. [16] As electron transfer mediators, FMN and FAD accept two electrons from NAD(P)H and transfer one electron to metal centres in heme-containing proteins, nonheme iron, or molybdenum sites. However, the transfer of electrons between reduced pyridine - dinucleotide cofactors is slow under physiological conditions and must be catalysed by enzymes. Function of these enzymes was mimicked by a modification of the cofactor by a recognition site for its counterpart and, thus, efficient electron transfer was enabled directly. Functionalised 1,4-dihydronicotinamides bearing a recognition unit for flavins were synthesised (Scheme 18). 

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