Bioorganic chemistry: Determination of enzyme mechanisms and transition states; synthesis of inhibitors, alternative substrates, and isotopically labeled compounds; enzyme kinetics
672 Natural Sciences Complex
Buffalo NY, 14260
Phone: (716) 645-4249
Fax: (716) 645-6963
The primary goal of research in the Murkin Laboratory is to understand the mechanisms of enzymatic processes related to disease and to construct models of their transition states, which may serve as blueprints for drug design. This “rational approach” has proven effective in the development of powerful enzyme inhibitors that have been successful in clinical treatments of human disorders. Our research aims to conquer these biological challenges while simultaneously addressing fundamentals of enzyme theory.
Transition-state structures are determined using multiple kinetic isotope effects (KIEs), which are measures of the bonding changes a substrate undergoes as it traverses through the transition state of a reaction. A transition-state model is generated by matching experimental KIEs to those calculated using computation. This model serves as a blueprint for the design of transition-state analogues, which are among the most powerful inhibitors in nature.
In the Murkin Laboratory, students will gain expertise in many of the chemical, biochemical, and biophysical tools essential for pursuing careers in academia or industry. Among these methods are protein expression, enzyme kinetics, and synthesis of inhibitors and isotopically labeled compounds. Projects in our lab are directed at drug targets in infectious diseases including malaria, tuberculosis, and bacterial infections.
* Authors contributed equally