Enzyme Mimicking

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. 

In Section 4.8 we discussed new options for the selective binding of cations and anions that arose because of the discovery of crown ethers. Now we shall continue the discussion of this topic with more emphasis given to its relevance to enzyme mimicking. 

This work on organic reaction mechanisms and our development of cyclophane chemistry were of great use to us in our later work. We did not shy away from tackling either multistep syntheses (up to 30 reactions) or highly asymmetric, designed systems needed in our studies of enzyme-mimicking systems. We needed both equilibria and kinetic techniques and an understanding of the importance of solvent effects in our more recent studies. 

For designing enzyme-mimicking catalysts exploiting metal ions as catalytic centers, it is necessary to understand catalytic repertories (32, 33) of metal ions acting as Lewis acid catalysts in the hydrolysis of peptide bonds and related carboxyl derivatives (e.g., esters). Although esters are much easier to hydrolyze than peptides, important mechanistic information for catalysis in peptide hydrolysis can be obtained from that in ester hydrolysis. 

Schulz-Ekloff G, Lipski RJ, Jaeger NI, Hulstede P, Kubelkova L (1995) Catal Lett 30 65 Parton R, den Vos D, Jacobs PA (1992) Enzyme mimicking with zeolites. In Derouane et al. (eds) Zeolites zeolite microporous solids synthesis, structure, and reactivity. Kluwer, Dordrecht, p 555 Herron N (1988) J Coord Chem 19 25... 

The cyclodextrins were the first compounds that have been studied with regard to their complexing and catalytic — in other words enzyme mimicking — properties. The enzymatic catabolism of starch mainly yields a-, p-, and y-cyclodextrin (CyD, 1-3). Those are macrocyclic oligosaccharides, in which six (a), seven (P) and eight (y) a-D-glucopyranose units, respectively, are connected by 1,4-glycosidic bonds. 

The calixarenes have a flexible or rigid cavity, resp., which can be shaped to some extent. Some inclusion compounds in the solid state have bren described, but the low solubility in water did not allow applications in respect to an enzyme mimick as yet. Host/guest interactions in solution according to studies of Gutsche et al. seem to occur in some cases, but are weak. Shinkai and coworkers seem recently to have overcome parts of these problems by incorporation of sulfonic add groups in this skeleton (72 and 73). 

The progress in this field as reported above already today shows that research on receptor and enzyme mimick chemistry in water solution has just started. It will be most interesting which of the perspectives mentioned before will be reached and which novel goals will be attractive in future. 

Leonhardt, A. Mosbach, K. Enzyme-mimicking polymers exhibiting specific substrate binding and catalytic functions. React. Polym., Ion Exch., Sorbents 1987, 6, 285-290. 

Furthermore, the postsynthetic modification of MOFs, either at the organic linkers or at the inorganic clusters [77, 136-139], is the best tool to open new possibilities to design efficient confined catalytic systems having defined single active site and fiexibility to accommodate substrates in a specific orientation in one word, the fine tuning of MOFs allows enzyme mimicking. 

Enzyme-mimicking systems that contain metal cations have also been designed. A very elegant supramolecular assembly was designed by Sanders et al.I l (see Fig. 7.11). They constructed trimeric porphyrin structures where Zn " " porphyrin moieties function as templates for the organization of substrates into a conformationaUy optimal configuration that undergoes an efficient acyl-transfer reaction or that lead to Diels Alder products. 

Additional reviews on biomimetic catalytic systems are available[20,21]. Shilov l reviews transition-metal complex systems that have related activities to biocatalytic systems. The review by de Vos et al.P l compares the reactivities of zeolite and layered hydroxide-based enzyme-mimicking systems. 

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. 

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