Enzyme models, cyclodextrins

Recent examples of artificial enzyme models based on the P-cyclodextrin skeleton ... 

Cyclodextrins as catalysts and enzyme models It has long been known that cyclodextrins may act as elementary models for the catalytic behaviour of enzymes (Breslow, 1971). These hosts, with the assistance of their hydroxyl functions, may exhibit guest specificity, competitive inhibition, and Michaelis-Menten-type kinetics. All these are characteristics of enzyme-catalyzed reactions. 

The highly evolved catalyst 20 combines several features that have proved successful in simpler cases. The ionic sulfonate groups make the substrate sufficiently soluble for the reaction to be run in water. (The four hydrophilic cyclodextrins perform the same service for the catalyst.) The target reaction, the seledive oxidation of the steroid skeleton, goes back to the early days of enzyme models,1711 and the choice of porphyrin and of manganese as the metal cation are based on many years experience. The aryl groups are perfluorinated because an earlier version of the catalyst suffered self-oxidation. 

Cyclodextrins are doughnut-shaped, macrocyclic oligosaccharides constructed of glucose units linked by a a(l - 4) bond. Hexamer, heptamer, and octamer are the most common, often called the a-, / -, and y-cyclodextrins, respectively (Fig. 1). Although cyclodextrin has been known as one of the oligoglucoses produced by Bacillus macerans since 1891 (2), its spectacular behavior as the possible enzyme model was first observed by Cramer and his co-worker (J). 

Cyclodextrin has the following apparent merits as an enzyme model ... 

Cyclophanes has several great advantages in use as enzyme models. First, the design of the preparation of substituted cyclophanes is well established. Second, they are very stable, even more by stable comparison with corresponding cyclodextrins. Moreover, a cyclophane of certain cavity size is readily available. Because of these advantages, cyclophanes attract increasing attention from chemists. 

In order to prepare certain excellent and sophisticated enzyme models, preparation of cyclodextrins having one or more functional groups is essential. At the same time, firm experimental evidence for their structures should be provided. 

The most difficult problem in the design of the enzyme model clearly lies in the difficulty of specific introduction of the functional groups into the host skeleton. For example, preparation of an enzyme model by use of fi-cyclodextrin often requires the introduction of two or more functional groups at certain positions among 7 primary (C6) and 14 secondary (C2 and C,) reactive positions. Unless one expects an accidental success by the use of any nonspecific functionalization, it is inevitably necessary for the host design to solve these problems. 

Thus, in the present stage, we can freely design an enzyme model by the use of cyclodextrin, although introduction of intermediate numbers of functional groups on cyclodextrin is not very easy. 

We now can prepare, in principle, enzyme models by use of the concept of host design, where artificial enzymes are so designed as multiple recognition hosts schematically shown in Fig. 20. Although unsubstituted cyclodextrins are well known to catalyze some organic reactions such as ester hydrolysis, their catalytic activities are relatively small. Recent progress in cyclodextrin chemistry has shown that it is possible to enhance the catalytic... 

Preparation and catalysis of disubstituted cyclodextrin as an excellent enzyme model is demonstrated by the RNAase model reported by Breslow et al. (68, 83). The enzyme models 10 and II, derived from 1, show a bellshaped pH versus rate profile for the hydrolysis of the cyclic phosphate of 4-terf-butylcatechol, indicating the cooperative catalysis by two imidazole groups (Fig. 21). The reactions catalyzed by 10 and II give exclusively 12 and 13, respectively. This interesting specificity indicates that the geometry of the P—O bond cleavage is quite different from each other. Another interesting enzyme-like kinetic behavior that these hosts exhibited is successful demonstration of the so-called bell-shaped pH profile. 

Another interesting enzyme model obtained by use of difunctionalized cyclodextrin having two imidazole groupings also afforded carbonic an-hydrase models as reported by the authors (69). Carbonic anhydrase has Zn2 + surrounded by three imidazoles in the active site and COz is bound to the active site is close proximity to Zn2+ with the assistance of hydrophobic... 

Introduction of a single catalytic group in cyclodextrin generally affords enzyme models as shown in many examples listed in Table XVI. Thus, reasonable acceleration and substrate specificity were observed in these models. However, monosubstituted cyclodextrins seem to have limitations and introduction of two or more functional groups is usually necessary for multiple recognition and for a sophisticated enzyme model. 

Cyclodextrins, also called cycloamylases, doughnut-shaped oligosaccharides, have attracted much attention as enzyme models. Although this area of research was surveyed in Volume 23, much subsequent progress in this field through multifunctionalization of cyclodextrin necessitates a new review. This contribution was written by I. Tabushi and Y. Kuroda, active researchers in this area. 

Catalytical aspects of supramolecular chemistry will be discussed in some detail in the next chapter. In this section only cyclodextrins as enzyme models will be briefly presented. Several examples of cyclodextrins catalytic activity have been reported. The acceleration of the reaction rate upon adding of CDs is... 

A benzoyl benzoate substituent in 6-position of p-cyclodcxtrine can act as redox catalyst for the cathodic cleavage of a benzylester-cyclodextrine inclusion compound. Thus, a simple redox enzyme model was formed... 

In cases where the natural amino acid side chains of enzymes are insufficient to carry out a desired reaction, the enzyme frequently uses coenzymes. A coenzyme is bound by the enzyme along with the substrate, and the enzyme catalyses the bimolecular reaction between the coenzyme and the substrate (cf. Section 2.6.3). A simple model for a-amino acid synthesis by transamination was developed by substituting /I-cyclodextrin with pyridoxamine. Pyridoxamine is able to carry out the transformation of a-keto acids to a-amino acids even without the presence of the cyclodextrin, but with the cyclodextrin cavity as well, the enzyme model proves to be more selective and transaminates substrates with aryl rings bound strongly by the cyclodextrin much more rapidly than those having little affinity for the cyclodextrin. Thus (p-le/f-butylphenyl) pyruvic acid and phenylpyruvic acid are transaminated respectively 15 000 and 100 times faster then pyruvic acid itself, to give (p-le/f-butylphenyl) alanine and phenylalanine (Scheme 12.5). 

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