Recent advancements in mass spectrometry for higher order structure characterization of protein therapeutics

Molecular characterization of higher order structure (HOS) in protein therapeutics is crucial to the selection of candidate molecules, understanding of structure-function relationships, formulation development, stability assessment, and comparability studies. Recent advances in mass spectrometry (MS), including native MS, hydrogen/deuterium exchange (HDX)-MS, and fast photochemical oxidation of proteins (FPOP) coupled with MS, have provided orthogonal ways to characterize HOS of protein therapeutics. In this review, we present the utility of native MS, HDX-MS and FPOP-MS in protein therapeutics discovery and development, with a focus on epitope mapping, aggregation assessment, and comparability studies. We also discuss future trends in the application of these MS methods to HOS characterization.

Automated summary

Molecular characterization of higher order structure in protein therapeutics is essential for various aspects in drug discovery and development. Recent advances in mass spectrometry offer orthogonal ways to characterize this structure and can be utilized for epitope mapping, aggregation assessment, and comparability studies. Future trends in applying these MS methods to HOS characterization are also discussed.