Hydrogen exchange-mass spectrometry (HX-MS) for analysis of higher-order structure of protein therapeutics across the pharmaceutical pipeline

Over the past three decades, hydrogen exchange-mass spectrometry (HX-MS) has advanced from an esoteric research tool to a highly repeatable analytical method sensitive to subtle changes in the higher-order structures of proteins. The method is now widely employed in drug discovery and vaccine development for the mapping of conformational epitopes. More recent work suggests that HX-MS data might also provide support in development and with regulatory considerations. My 58^th semester talk will begin with a brief overview of what is measured in HX-MS and how results are interpreted. Some examples of our recent work will illustrate some of the potential applications pharmaceutical discovery and development:

1. Broad characterization of the epitopic surface of antigens from Borrelia burgdorferi, the causative agent of Lyme disease
2. Mapping effects of preservatives and other excipients on aggregation hotspots on monoclonal antibody therapeutics
3. Development of an analytical-statistical framework to evaluate structural equivalence of therapeutic proteins and their biosimilars