期刊
EXPERT OPINION ON DRUG DISCOVERY
卷 12, 期 10, 页码 981-994出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17460441.2017.1363734
关键词
Hydrogen-deuterium exchange mass spectrometry; HDX-MS; hydrogen deuterium exchange; HDX; protein dynamics; epitope mapping; bio-therapeutics; drug development; allostery
资金
- Institute of Infection and Immunity of the Canadian Institutes of Health Research [FRN 142393]
- Natural Sciences and Engineering Research Council of Canada [NSERC-2014-05218]
- Medical Research Council [MC_U105184308]
- St Catharine's College, Cambridge
- MRC [MC_U105184308] Funding Source: UKRI
Introduction: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful methodology to study protein dynamics, protein folding, protein-protein interactions, and protein small molecule interactions. The development of novel methodologies and technical advancements in mass spectrometers has greatly expanded the accessibility and acceptance of this technique within both academia and industry. Areas covered: This review examines the theoretical basis of how amide exchange occurs, how different mass spectrometer approaches can be used for HDX-MS experiments, as well as the use of HDX-MS in drug development, specifically focusing on how HDX-MS is used to characterize bio-therapeutics, and its use in examining protein-protein and protein small molecule interactions. Expert opinion: HDX-MS has been widely accepted within the pharmaceutical industry for the characterization of bio-therapeutics as well as in the mapping of antibody drug epitopes. However, there is room for this technique to be more widely used in the drug discovery process. This is particularly true in the use of HDX-MS as a complement to other high-resolution structural approaches, as well as in the development of small molecule therapeutics that can target both active-site and allosteric binding sites.
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