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Conformational changes in oxidatively stressed monoclonal antibodies studied by hydrogen exchange mass spectrometry.


ABSTRACT: Oxidation of methionine residues in biopharmaceuticals is a common and often unwanted modification that frequently occurs during their manufacture and storage. It often results in a lack of stability and biological function of the product, necessitating continuous testing for the modification throughout the product shelf life. A major class of biopharmaceutical products are monoclonal antibodies (mAbs), however, techniques for their detailed structural analysis have until recently been limited. Hydrogen/deuterium exchange mass spectrometry (HXMS) has recently been successfully applied to the analysis of mAbs. Here we used HXMS to identify and localise the structural changes that occurred in a mAb (IgG1) after accelerated oxidative stress. Structural alterations in a number of segments of the Fc region were observed and these related to oxidation of methionine residues. These included a large change in the hydrogen exchange profile of residues 247-253 of the heavy chain, while smaller changes in hydrogen exchange profile were identified for peptides that contained residues in the interface of the C(H)2 and C(H)3 domains.

SUBMITTER: Burkitt W 

PROVIDER: S-EPMC2867022 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Conformational changes in oxidatively stressed monoclonal antibodies studied by hydrogen exchange mass spectrometry.

Burkitt William W   Domann Paula P   O'Connor Gavin G  

Protein science : a publication of the Protein Society 20100401 4


Oxidation of methionine residues in biopharmaceuticals is a common and often unwanted modification that frequently occurs during their manufacture and storage. It often results in a lack of stability and biological function of the product, necessitating continuous testing for the modification throughout the product shelf life. A major class of biopharmaceutical products are monoclonal antibodies (mAbs), however, techniques for their detailed structural analysis have until recently been limited.  ...[more]

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