Rapid antibody conformational screening by matrix‐assisted laser desorption/ionization hydrogen‐deuterium exchange mass spectrometry

Abstract

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.

Accelerating Pharmaceutical Process Development with an Acoustic Droplet Ejection-Multiple Reaction Monitoring-Mass Spectrometry Workflow

“…27−31 Makarov's group has recently combined MALDI-time-offlight (TOF)-MS with hydrogen−deuterium exchange (HDX) to rapidly screen for protein conformational changes in solution. 32,33 The same group also introduced liposomebased approach permeability assay (LAMPA) 34 and cellbased approach membrane permeability assay (CAMPA) 35 via MALDI-HDX-MS to study peptide drug permeability in a label-free and ultrahigh-throughput manner. Cooks' group pioneered several generations of DESI-MS platforms to screen organic reactions and enzymatic bioassays.…”

“…Makarov’s group has recently combined MALDI-time-of-flight (TOF)-MS with hydrogen–deuterium exchange (HDX) to rapidly screen for protein conformational changes in solution. , The same group also introduced liposome-based approach permeability assay (LAMPA) and cell-based approach membrane permeability assay (CAMPA) via MALDI-HDX-MS to study peptide drug permeability in a label-free and ultrahigh-throughput manner. Cooks’ group pioneered several generations of DESI-MS platforms to screen organic reactions and enzymatic bioassays. − Kennedy’s group developed droplet microfluidics MS methods for the analysis of pharmaceutically relevant small molecules and proteins. − Welch and Regalado’s groups introduced numerous high-throughput LC-MS assays enabling nanomole-scale high-throughput chemistry, biocatalysis, and other pharmaceutical PR&D endeavors. ,, …”