Investigating monoclonal antibody aggregation using a combination of H/DX-MS and other biophysical measurements.
Investigating monoclonal antibody aggregation using a combination of H/DX-MS and other biophysical measurements.
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DOI：
10.1002/jps.23754
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发表时间：
2013-12
影响因子：
3.8
通讯作者：
Houde, Damian
中科院分区：
文献类型：
--
作者：
Iacob, Roxana E.;Bou-Assaf, George M.;Makowski, Lee;Engen, John R.;Berkowitz, Steven A.;Houde, Damian
关键词：
为了确定抗体的结构变化如何与聚集相关，必须确定抗体易于聚集和/或受聚集影响的结构区域。在这项工作中，将两种不同单克隆抗体 (mAb) 单体的高阶结构和生物物理特性与其最简单的聚集形式（即在正常生产和储存条件下自然发生的二聚体）进行了比较。结合氢/氘交换质谱（H/DX-MS）和其他生物物理测量进行比较。结果表明，其中一种 mAb 单体 (mAb1) 的二聚过程在单体和二聚体形式之间的氘吸收方面没有差异。然而，另一种 mAb 单体 (mAb2) 与其二聚体形式相比，在氢氘交换方面表现出细微的变化。在这种情况下，观察到的差异位于 CH2 结构域的特定功能区域以及 CH1 和 CH2 结构域之间的铰链区。讨论了这些变化对抗体结构和聚集机制的重要性和影响。
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 was compared to their simplest aggregated form, i.e., dimers that naturally occurred during normal production and storage conditions. A combination of hydrogen/deuterium exchange mass spectrometry (H/DX-MS) 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 compared to its dimer form. In this case, differences observed were located in specific functional regions of the CH2 domain and the hinge region between CH1 and CH2 domains. The importance and the implications of these changes on the antibody structure and mechanism of aggregation are discussed.
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影响因子：
2
作者：
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通讯作者：
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影响因子：
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DOI：
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