Hydrogen deuterium exchange mass spectrometry in biopharmaceutical discovery and development - A review.
Protein therapeutics have emerged as a major class of biopharmaceuticals over the past several decades, a trend that has motivated the advancement of bioanalytical technologies for protein therapeutic characterization. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful and sensitive technique that can probe the higher order structure of proteins and has been used in the assessment and development of monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs) and biosimilar antibodies. It has also been used to quantify protein-ligand, protein-receptor and other protein-protein interactions involved in signaling pathways. In manufacturing and development, HDX-MS can validate storage formulations and manufacturing processes for various biotherapeutics. Currently, HDX-MS is being refined to provide additional coverage, sensitivity and structural specificity and implemented on the millisecond timescale to reveal residual structure and dynamics in disordered domains and intrinsically disordered proteins.
Chemistry Department, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada; The Centre for Research in Mass Spectrometry, York University, Toronto, ON, M3J1P3, Canada. Electronic address: dengbin@yorku.ca.
Bin
B
Deng
Chemistry Department, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada; The Centre for Research in Mass Spectrometry, York University, Toronto, ON, M3J1P3, Canada. Electronic address: clento@yorku.ca.
Cristina
C
Lento
Chemistry Department, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada; The Centre for Research in Mass Spectrometry, York University, Toronto, ON, M3J1P3, Canada. Electronic address: dkwilson@yorku.ca.
Derek J
DJ
Wilson
D001702:Biopharmaceutics; D003903:Deuterium / Q000737:chemistry*; D055808:Drug Discovery; D006859:Hydrogen / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*
D006859:Hydrogen; D003903:Deuterium
Biopharmaceutical industry; Biosimilar; Drug discovery and development; Hydrogen deuterium exchange; Mass spectrometry; Protein therapeutics