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Higher order structure characterization of protein therapeutics by hydrogen/deuterium exchange mass spectrometry

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Abstract

Characterization of therapeutic drugs is a crucial step in drug development in the biopharmaceutical industry. Analysis of protein therapeutics is a challenging task because of the complexities associated with large molecular size and 3D structures. Recent advances in hydrogen/deuterium-exchange mass spectrometry (HDX-MS) have provided a means to assess higher-order structure of protein therapeutics in solution. In this review, the principles and procedures of HDX-MS for protein therapeutics characterization are presented, focusing on specific applications of epitope mapping for protein–protein interactions and higher-order structure comparison studies for conformational dynamics of protein therapeutics.

HDX of protein backbone amide hydrogen

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Acknowledgements

The authors thank Dr Adrienne Tymiak, Dr Bruce Car, Dr Morrey Atkinson, and Dr Peter Moesta from Bristol-Myers Squibb for their support of this project.

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Authors and Affiliations

  1. Bioanalytical and Discovery Analytical Sciences, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08543, USA

    Richard Y.-C. Huang & Guodong Chen

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  1. Richard Y.-C. Huang
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  2. Guodong Chen
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Correspondence to Guodong Chen.

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Published in the topical collection Analysis of Biological Therapeutic Agents and Biosimilars with guest editor Karen Phinney.

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Huang, R.YC., Chen, G. Higher order structure characterization of protein therapeutics by hydrogen/deuterium exchange mass spectrometry. Anal Bioanal Chem 406, 6541–6558 (2014). https://doi.org/10.1007/s00216-014-7924-3

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  • DOI: https://doi.org/10.1007/s00216-014-7924-3

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