Richard A. Lerner
Wolf Prize Laureate in Chemistry 1994/5
Affiliation at the time of the award:
Scripps Research Institute, USA
“for converting antibodies into enzymes, thus permitting the catalysis of chemical reactions considered impossible to achieve by classical chemical procedures”.
Dr. Richard A. Lerner and Professor Peter G. Schultz independently and almost simultaneously in 1986, conceived and demonstrated the idea that antibodies could selectively catalyze chemical reactions. Lerner´s research group raised antibodies against negatively charged phosphate transition-state analogues, and showed that these selectively catalyzed the hydrolysis of carbonates. Schultz´s group did likewise with phosphonates, thereby hydrolysing esters. Their recognition of the importance of the transition state in the thermodynamics and kinetics of enzyme reactions, and the understanding of the diversity of the immune system, were essential to the development of this advance.
The earliest experiments involved simple reactions with well-studied mechanisms. Since that pioneering event antibodies have been developed that catalyze a wide range of chemical and biological reactions. Recent work, under the separate leadership of Lerner and of Schultz, has focused on selective chemical transformations that are difficult to achieve by existing chemical methods. These include disfavoured chemical reactions, reactions along one of many nearly equivalent reaction coordinates, and reactions in which the inherent reactivity or molarity of the reactants is reversed. In each case the binding energy of the immunogen and the antibody was used to accelerate and control the reaction. The specificity, and in some cases the rates, of these antibody catalyzed reactions rival those of natural enzymatic reactions, which have only reached their high efficiency through the slow processes of evolution.
This work is of high importance for the future of synthetic organic chemistry. It is a marvellous illustration of how a deep knowledge of biological processes, combined with very sophisticated chemistry, produced a result which practitioners in only one of these two disciplines would have been unlikely to reach.