期刊
ANALYTICA CHIMICA ACTA
卷 940, 期 -, 页码 8-20出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.aca.2016.08.006
关键词
Hydrogen deuterium exchange; Mass spectrometry; Drug discovery and development; Protein therapeutics; Biosimilar; Biopharmaceutical industry
资金
- Natural Sciences and Engineering Research Council (NSERC) of Canada Discovery Program [504027]
- Engage Program [492095-15]
- Collaborative Research and Development (CRD) Program [485321-15]
- Krembil Foundation
- Canadian Alzheimer's Society
- Mathematics of Information Technology and Complex Systems (MITACS)
- Ontario Ministry of Research and Innovation (MRI)
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, HDXMS 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. (C) 2016 Elsevier B. V. All rights reserved.
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