Advances in Bioanalytics and Biomarkers

Label Free Approaches to Quantify Small Molecule-Receptor Binding

Monday, February 5
11:00 AM - 11:30 AM
Location: 6E

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Ligand-receptor binding assays are commonly employed to study the thermodynamics and kinetics of receptor-ligand interactions. Conventional binding assays use labeled ligands which can be resource-intensive to prepare and are not always suitable. We have developed label-free LC-MS based assays to quantitate small molecule binding to both soluble and membrane associated proteins. In direct binding mode, the methodology enables rapid assessment of ligand affinity to its molecular target as well as the concentration of the bound ligand. Structure-activity relationships can also be assessed in competition binding mode. This presentation will describe the experimental design, validation and application of equilibrium-based, direct and competition binding assays using LC-MS for bound ligand quantitation, and the utility of the method for assessing binding kinetics.

David G. McLaren

Director
Merck & Co, Inc.

David earned his B.Sc. in Chemistry from the University of Manitoba, Canada and his Ph.D. in Analytical Chemistry from the University of British Columbia. David joined Merck Research Labs in 2009 as a Scientist in the cardiometabolic disease department where he applied mass spectrometry to support the development of exploratory and translational biomarkers. He is presently a Director in the Screening & Compound Profiling Department, where he leads a team of analytical chemists and is responsible for mass spectrometry operations. His current interests include label-free screening by high-throughput MS and biophysical characterization of protein-ligand interactions using techniques such as ion mobility and hydrogen-deuterium exchange. Dr. McLaren has published more than 40 papers, invited reviews and book chapters and has presented at several international conferences on the use of mass spectrometry in drug discovery and development.

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