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Characterization of Aggregation Propensity of a Human Fc-Fusion Protein Therapeutic by Hydrogen/Deuterium Exchange Mass Spectrometry |
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| Authors: | Richard Y-C Huang Roxana E Iacob Stanley R Krystek Mi Jin Hui Wei Li Tao Tapan K Das Adrienne A Tymiak John R Engen Guodong Chen | |
| Institution: | 1.Bioanalytical and Discovery Analytical Sciences, Research and Development,Bristol-Myers Squibb Company,Princeton,USA;2.Department of Chemistry and Chemical Biology,Northeastern University,Boston,USA;3.Molecular Structure and Design, Research and Development,Bristol-Myers Squibb Company,Princeton,USA;4.Biologics Development and Operations, Global Manufacturing & Supply,Bristol-Myers Squibb Company,Syracuse,USA;5.Biologics Development and Operations, Global Manufacturing & Supply,Bristol-Myers Squibb Company,Hopewell,USA | |
| Abstract: | Aggregation of protein therapeutics has long been a concern across different stages of manufacturing processes in the biopharmaceutical industry. It is often indicative of aberrant protein therapeutic higher-order structure. In this study, the aggregation propensity of a human Fc-fusion protein therapeutic was characterized. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) was applied to examine the conformational dynamics of dimers collected from a bioreactor. HDX-MS data combined with spatial aggregation propensity calculations revealed a potential aggregation interface in the Fc domain. This study provides a general strategy for the characterization of the aggregation propensity of Fc-fusion proteins at the molecular level. Graphical Abstract | |
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