A new strategy for the generation of catalytic antibodies.
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 reactions, carbon-carbon bond forming and carbon-carbon bond cleaving reactions. In addition, a number of strategies are emerging for the generation of catalytic antibodies including transition state stabilization, catalysis by approximation, and the introduction of catalytic groups or cofactors into antibody combining sites. 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 antibody can be exploited to generate catalytic amino-acid side chains in an antibody-combining site. The antibody-catalysed reaction, a beta-elimination reaction, exhibits saturation kinetics, substrate specificity, competitive inhibition by hapten, and specific inactivation by a reagent that modifies carboxylate residues.
Shokat
K M
KM
Department of Chemistry, University of California, Berkeley 94720.
Leumann
C J
CJ
Sugasawara
R
R
Schultz
P G
PG
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001666:Binding Sites, Antibody; D002384:Catalysis; D006241:Haptens; D006863:Hydrogen-Ion Concentration
D000906:Antibodies; D000911:Antibodies, Monoclonal; D006241:Haptens