Catalytic Antibodies

The study of catalytic antibodies combines both chemistry and immunology. The first investigations involving chemical reactions catalyzed by antibodies were published in 1986. It was during that particular year that the research groups of Schultz and Lerner raised antibodies to tetrahedral, negatively charged phosphate and phosphonate transition state analogs. These analogs were then used to catalyze the hydrolysis of carbonates and esters, respectively (Leumann, 1993, p. 1291).

Catalytic antibodies are derived from chemically stable hapten. These haptens typically mimic the structure and electronic properties of a given reaction's transition state; they are hence synthetic analogs of the transition state. They give their hapten-derived antibodies the ability to bind specific ligands with high aff

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turnover rate, nearly all of an antibody's binding force may be directed towards reaction facilitation. This energy may then be used to generate nonnatural chemical reactions. Accordingly, Danishefsky (1993) goes on to delineate the various organic reactions to which the techniques have been applied. These include, for example, the Claisen rearrangement and the Diels-Alder reaction (Danishefsky, 1993, p. 469). Some of the earliest chemical processes to employ catalytic antibodies did not actually require catalysis. Researchers primarily focused on reactions that might be sensitive to such antibody effects as induced strain and proximity. Hilvert, Carpenter, Nared, & Auditor (1988), for example, used catalytic antibodies to facilitate the Claisen rearrangement. The Claisen rearrangement has particular biological relevance. In bacteria, fungi, and the higher plants, it is essential for the biosynthesis of aromatic amino acids (Hilvert et al., 1988, p. 4953-4955). Hilvert et al. (1988) generated antibodies against a transition state analog of chorismate mutase. These catalytic antibodies were then used to catalyze the rearrangement of chorismate to phrenate. Compared to the uncatalyzed reaction, rate accelerations of more
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