LAUSR

Recent advances in the field of cancer biology have accelerated the discovery and development of novel biopharmaceuticals. At the forefront of these drug development efforts are high-throughput screening, compressed timelines and limited sample quantities, all characteristic of the discovery space. To meet program targets, large numbers of protein variants must be produced, screened, and characterized, presenting a daunting analytical challenge. Additionally, higher-order structure is paramount for protein function and must be monitored as a critical quality attribute. Matrix Assisted Laser Desorption Ionization MS has been utilized as an ultra-fast, automatable, sample-sparing analytical tool for biomolecules. Our group has published applications integrating Hydrogen-Deuterium Exchange MS with Matrix Assisted Laser Desorption Ionization MS for the rapid conformational characterization of small proteins, the current work expands this application to monoclonal and bi-specific antibodies. This study demonstrates the ability of the methodology Matrix Assisted Laser Desorption Ionization Hydrogen-Deuterium Exchange MS to detect conformational differences between bi-specific antibodies from different expression host. These conformational differences were validated by orthogonal techniques including Circular Dichroism, Nuclear Magnetic Resonance and Size-Exclusion Chromatography Hydrogen-Deuterium Exchange MS. This work demonstrates the utility of applying the developed methodology as a rapid conformational screening tool to triage samples for further analytical characterization. This article is protected by copyright. All rights reserved.