CATALYTIC ANTIBODIES - MECHANISTIC AND PRACTICAL CONSIDERATIONS

Studies of catalytic antibodies have provided examples of mechanisms ranging from simple transition-state stabilization to multi-step pathways involving covalent intermediates. This review critically compares catalytic antibodies with other biological catalysts, using amide and ester hydrolysis as examples. By means of kinetic simulations, the catalytic efficiencies of many of these antibodies are shown to be limited by a number of factors including relatively weak substrate recognition coupled with relatively strong product binding. This analysis also suggests specific methods to improve catalytic antibodies, either through more sophisticated transition-state analogue design or by mutagenesis of existing antibodies.