Catalytic antibodies: new developments

Abstract

Both antibodies and enzymes can specifically recognize and bind other molecules. In the case of enzymes and of antibodies ellicited against a transition state analogues of a reaction, binding is followed by catalysis. The first catalytic antibodies were generated against phosphonate-containing transition-state analogues, and catalysed hydrolytic reactions. Since those reports, antibody catalysis was shown to be feasible for many different types of reactions. Evidence has been presented that factors other than stabilization of the transition state can contribute to catalysis. These insights can be employed in the design of haptens. An alternative and complementary approach to the generation of catalytic antibodies is modification of antibodies, either by chemical introduction of catalytic groups or by site-directed mutagenesis. Potential applications of catalytic antibodies can be envisaged in the fields of analytical chemistry and medicine and as catalysts in the chemical industry. The limited availability of antibodies still hampers their application, but rapid progress is being made in the cloning of antibody fragments in a variety of host systems, e.g. Escherichia coli, yeast, hybridomas and plants. The expression of a combinatorial library of antibody heavy- and light-chain fragments in phage λ permits the screening of large numbers of antibodies that possess the desired binding or catalytic properties, and might eventually make immunization of animals redundant.