Hydrogen/deuterium exchange mass spectrometry for probing higher order structure of protein therapeutics: methodology and applications
Drug Discovery TodayPublished 6 August 2013Open access
Hui Wei, Jingjie Mo, Liyuan Tao, Reb J. Russell, Adrienne A. Tymiak, Guodong Chen
Citations201
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TL;DR
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.
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.
Keywords
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Journal of Medicinal ChemistryA Medicinal Chemist’s Guide to Molecular Interactions
1,697 Citations2010Caterina Bissantz, Bernd Kuhn +1 more
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Journal of Biological ChemistryEffect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase.
1,263 Citations1977Abraham Abuchowski, Judy McCoy +3 more
Methoxypolyethylene glycols and catalase modified by covalent attachment of PEG-1900 to 43% of the amino groups exhibited enhanced circulating lives in the blood of acatalasemic mice during repetitive intravenous injections and no evidence of tissue or organ damage was seen.
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Journal of the American Chemical SocietyIntramolecular Migration of Amide Hydrogens in Protonated Peptides upon Collisional Activation
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167 Citations1979Joseph J. Rosa, Frederic M. Richards
A method is described which extends the structural resolution of the usual hydrogen-exchange experiment by quantifying the exchange kinetics from known regions of a protein by measuring total protein-bound radioactivity at various specified times.
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