Critical analysis of antibody catalysis

Antibody molecules elicited with rationally designed transition-state analo gs catalyze numerous reactions, including many that cannot be achieved by s tandard chemical methods. Although relatively primitive when compared with natural enzymes, these catalysts are valuable tools for probing the origins and evolution of biological catalysis. Mechanistic and structural analyses of representative antibody catalysts, generated with a variety of strategi es for several different reaction types, suggest that their modest efficien cy is a consequence of imperfect hapten design and indirect selection. Deve lopment of improved transition-stare analogs, refinements in immunization a nd screening protocols, and elaboration of general strategies for augmentin g the efficiency of first-generation catalytic antibodies are identified as evident, but difficult, challenges Tor this field. Rising to these challen ges and more successfully integrating programmable design with the selectiv e forces of biology will enhance our understanding of enzymatic catalysis. Further, it should yield useful protein catalysts for an enhanced range of practical applications in chemistry and biology.