Antibodies general acid/base catalysis

Antibody 15C5 was able to catalyse the hydrolysis of the triester [105] with cat 2.65 x 10 3 min 1 whilst a second antibody from the same immunization programme was later found to hydrolyse the acetylcholinesterase inhibitor Paraoxon [106] with kcat = 1.95 x 10 3min-1 at 25°C (Appendix entry 6.2) (Lavey and Janda, 1996b). Antibody 3H5 showed Michaelis-Menten kinetics and was strongly inhibited by the hapten [104]. It exhibited a linear dependence of the rate of hydrolysis on hydroxide ion concentration, suggesting that 3H5 effects catalysis by transition state stabilization rather than by general acid/base catalysis. 

Other approaches have been developed to generate catalytic antibodies including covalent catalysis, proximity effects, and general acid-base catalysis [7]. In addition, strategies have been developed to directly select immu-... 

It has further been demonstrated that by appropriate presentation of point charges on haptens, general acid/ base catalysis could be achieved in a variety of catalytic antibody reactions, including condensation, isomerization, elimination, and hydrolytic reactions. 

In Figure 3 a schematic view is presented of how primary catalysis is achieved. Besides this necessary and sufficient condition required to set up catalysis, there may be some other factors producing an enhancement of the catalytic event. General acid and general base catalytic groups, metal coordination sphere appropriately prepared are examples of catalytic subsidiary effects. The pure molding factor is usually achieved by catalytic antibodies techniques. 

The nature of antibody catalysis remains to be elucidated, and antibodies will not reach the efficiency of enzymes until they can emulate the conformational changes, acid/base, redox, and/or nucleophilic/electro-philic reactivities of catalytic residues along the entire reaction coordinate. It is worthy of note that Hollfelder et al recently demonstrated that serum albumins catalyze the eliminative ring-opening of a benzoisoxazole at rates that are similar to those observed with catalytic antibodies. They suggest that formal general base catalysis contributes only modestly to the efficiency of both systems, and they favor the view that the antibody catalysis may be enhanced in some cases by nonspecific medium effects. 

Pericyclic processes comprise a broad and important class of concerted reactions of both theoretical and practical interest. These transformations, which are especially useful in the construction of carbon-carbon bonds,93 include electrocyclic reactions, sigmatropic rearrangements, and cycloadditions. Because they are not typically subject to general acid-general base chemistry but can be highly sensitive to strain and proximity effects, they are attractive targets for antibody catalysis. 

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