Hydrogen/deuterium exchange mass spectrometry for probing higher order structure of protein therapeutics: methodology and applications

•Hydrogen/deuterium exchange mass spectrometry (HDX-MS) technology for assessment of higher order structure of protein therapeutics.•Methodology: global HDX-MS and peptide HDX-MS.•Applications: epitope mapping and comparability study. The higher order structure of protein therapeutics can be interro...

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Bibliographic Details
Published in:Drug discovery today 2014-01, Vol.19 (1), p.95-102
Main Authors: Wei, Hui, Mo, Jingjie, Tao, Li, Russell, Reb J., Tymiak, Adrienne A., Chen, Guodong, Iacob, Roxana E., Engen, John R.
Format: Article
Language:English
Subjects:
Animals
Deuterium - chemistry
Humans
Hydrogen - chemistry
Mass Spectrometry - methods
Protein Binding - physiology
Protein Interaction Maps - physiology
Protein Structure, Secondary
Protein Transport - physiology
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Summary:•Hydrogen/deuterium exchange mass spectrometry (HDX-MS) technology for assessment of higher order structure of protein therapeutics.•Methodology: global HDX-MS and peptide HDX-MS.•Applications: epitope mapping and comparability study. The higher order structure of protein therapeutics can be interrogated with hydrogen/deuterium exchange mass spectrometry (HDX-MS). HDX-MS is now a widely used tool in the structural characterization of protein therapeutics. In this review, HDX-MS based workflows designed for protein therapeutic discovery and development processes are presented, focusing on the specific applications of epitope mapping for protein/drug interactions and biopharmaceutical comparability studies. Future trends in the application of HDX-MS in protein therapeutics characterization are also described.
ISSN:1359-6446
1878-5832
DOI:10.1016/j.drudis.2013.07.019