期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 102, 期 12, 页码 4315-4329出版社
WILEY
DOI: 10.1002/jps.23754
关键词
Antibody dimerization; Protein aggregation; Chromatography; Electrophoresis; Hydrogen-deuterium exchange mass spectrometry (H; DX-MS); Calorimetry (DSC); Protein structure; Small-angle X-ray solution scattering (SAXS); Domain swapping
资金
- National Institute of Health [GM086507, GM 101135]
- Waters Corporation
- US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-98CH10886]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1158340] Funding Source: National Science Foundation
To determine how structural changes in antibodies are connected with aggregation, the structural areas of an antibody prone to and/or impacted by aggregation must be identified. In this work, the higher-order structure and biophysical properties of two different monoclonal antibody (mAb) monomers were compared with their simplest aggregated form, that is, dimers that naturally occurred during normal production and storage conditions. A combination of hydrogen/deuterium exchange mass spectrometry and other biophysical measurements was used to make the comparison. The results show that the dimerization process for one of the mAb monomers (mAb1) displayed no differences in its deuterium uptake between monomer and dimer forms. However, the other mAb monomer (mAb2) showed subtle changes in hydrogen/deuterium exchange as compared with its dimer form. In this case, differences observed were located in specific functional regions of the C(H)2 domain and the hinge region between C(H)1 and C(H)2 domains. The importance and the implications of these changes on the antibody structure and mechanism of aggregation are discussed. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4315-4329, 2013
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