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

Hui Wei; Jingjie Mo; Li Tao; Reb J Russell; Adrienne A Tymiak; Guodong Chen; Roxana E Iacob; John R Engen

doi:10.1016/j.drudis.2013.07.019

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

Drug Discov Today. 2014 Jan;19(1):95-102. doi: 10.1016/j.drudis.2013.07.019. Epub 2013 Aug 6.

Authors

Hui Wei¹, Jingjie Mo¹, Li Tao², Reb J Russell³, Adrienne A Tymiak¹, Guodong Chen⁴, Roxana E Iacob⁵, John R Engen⁶

Affiliations

¹ Bioanalytical and Discovery Analytical Sciences, Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
² Biologics Manufacturing and Process Development, Global Manufacturing and Supply, Bristol-Myers Squibb, Hopewell, NJ, USA.
³ Biologics Manufacturing and Process Development, Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, USA.
⁴ Bioanalytical and Discovery Analytical Sciences, Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: [email protected].
⁵ Department of Chemistry & Chemical Biology, Northeastern University, Boston, MA, USA.
⁶ Department of Chemistry & Chemical Biology, Northeastern University, Boston, MA, USA. Electronic address: [email protected].

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Deuterium / chemistry*
Humans
Hydrogen / chemistry*
Mass Spectrometry / methods*
Protein Binding / physiology
Protein Interaction Maps / physiology*
Protein Structure, Secondary
Protein Transport / physiology

Substances

Hydrogen
Deuterium

Abstract

Publication types

MeSH terms

Substances

Grants and funding