Abstract
THE high binding affinity and specificity of antibodies for a wide range of ligands has recently been exploited in the generation of catalysts for acyl-transfer reactions1–7, carbon-carbon bond forming8,9 and carbon-carbon bond cleaving reactions10. In addition, a number of strategies are emerging for the generation of catalytic antibodies including transition state stabilization1–6, catalysis by approximation7,8, and the introduction of catalytic groups or cof ac-tors into antibody combining sites10–13. An important goal in the design of catalytic antibodies is the development of general rules relating hapten structure to the corresponding catalytic groups in the antibody combining site. We report here that electrostatic interactions between a hapten and the complementary antibody14,15 can be exploited to generate catalytic amino-acid side chains in an antibody-combining site. The antibody-catalysed reaction, a β-elimination reaction, exhibits saturation kinetics, substrate specificity, competitive inhibition by hapten, and specific inactivation by a reagent that modifies carboxylate residues.
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Shokat, K., Leumann, C., Sugasawara, R. et al. A new strategy for the generation of catalytic antibodies. Nature 338, 269–271 (1989). https://doi.org/10.1038/338269a0
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DOI: https://doi.org/10.1038/338269a0
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