Cyclodextrin serine proteases

A good example of this is the classic work by Bender (6) on the reaction ofra-f-butylphenyl acetate. This substrate binds well into the cavity, and the substrate then undergoes an acetyl transfer reaction in which a cyclodextrin hydroxyl group is acetylated. The reaction can be compared with the first step in the action of a serine esterase, or a serine protease acting on an ester substrate. However, the acceleration of this acetyl transfer, compared with simple hydrolysis by the medium, was only 250-fold. 

Supramolecular catalysts using synthetic host molecules have been well researched. Early studies realized a hydrolysis reaction for ester derivatives using modified cyclodextrins (CDs). CDs are suitable for the study of two-substrate supramolecular catalysis and for the synthesis of artificial enzymes. 2-Benzyimidazoleacetic acid-modified a-cyclodextrin hydrolyzes m-tert-butylphenyl acetate at an accelerated rate. The imidazole has a benzoate group in a position that imitates the function of the aspartate ion with the catalytic triad characteristics of serine proteases such as chymotrypsin (Figure 12.1). ... 

M. L. Bender s group at Northwestern University studied the hydrolysis of t-butylphenyl acetate in the prescence of 2-benzimidazoleacetic acid (175) with a-cyclodextrin in order to probe the charge-relay system of the enzymatic mechanism in serine proteases. The results showed that in the presence of catalyst a 12-fold acceleration of ester cleavage takes place after complex formation between the substrate and a-cyclodextrin. This observation is consistent with the formation of the substrate-enzyme complex in... 

Breslow and collaborators used P-cyclodextrine as secondary binding (host) moiety to select substrates like an enzyme. They show in detailed studies that P-cyclodextrine and modified p-cyclodextrine catalyze the cleavage of esters, mimicking serine proteases in a very rudimentary way [14-20], Reaction conditions e.g. buffer, solvent, influence of the stmcture of the ester, and pressure effect the performance of the catalyst. In his reports he shows that P-cyclodextrine can enhance the rate of the acylation reactions by 10 -10 or better, compared to the uncatalyzed... 

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