Professor Richard B. Silverman of Northwestern University is the recipient of the 2024 Abeles and Jencks Award for the Chemistry of Biological Processes. His first publication with Dr. Abeles (“Inactivation of Pyridoxal Phosphate-Dependent Enzymes by Mono- and Polyhaloalanines”) set the stage for a truly distinguished career and a body of work that showed how mechanistic enzymology could be used to develop a drug by unravelling the fine details of the inactivation process and using these findings to make efficient and specific inactivators. PLP-dependent enzymes were long thought to be “undruggable” because so many enzymes use PLP that one could never achieve specificity, resulting in a host of adverse effects. Rick’s work is a model for the bench to bedside development of mechanism-based inhibitors of PLP-dependent enzymes. Among his many accomplishments, he invented Lyrica, the blockbuster drug marketed by Pfizer for epilepsy, fibromyalgia, and neuropathic pain. More are in the pipeline or in clinic trials.
Rick has been at Northwestern University since 1976. The field of enzymology has been bestowed with outstanding scientific talent. Those investigators who have not only elucidated the chemical mechanism of an enzyme but have rationally-designed molecules that cleverly exploit an enzyme’s mechanism to activate a pseudo-substrate that goes on to covalently inactivate the enzyme, known as mechanism-based inactivation, stand at the top of this field of study. Rick literally wrote the book on mechanism-based inactivators. Fittingly, Rick began studies on mechanism-based enzyme inactivation in the laboratory of Dr. Abeles. Professor Silverman is one of the stars from this legendary laboratory.
Story first published on October 9, 2023, by The ACS Division of Biological Chemistry.