Characterization of the basic charge variants of a human IgG1 Effect of copper concentration in cell culture media
Characterization of the basic charge variants of a human IgG1 Effect of copper concentration in cell culture media
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DOI：
10.4161/mabs.3.6.17959
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发表时间：
2011-11-01
期刊：
影响因子：
5.3
通讯作者：
Yan, Boxu
中科院分区：
文献类型：
--
作者：
Kaschak, Timothy;Boyd, Daniel;Yan, Boxu
我们报告了一个IgG1的案例研究，该IgG1具有由一条或两条重链上的c端脯氨酸酰胺化引起的独特的基本电荷变异谱。在细胞培养过程中，脯氨酸酰胺化对生产培养基中铜离子浓度敏感，Cu2+浓度越高，脯氨酸酰胺化检测水平越高。这一结论得到了样品分析的支持，从肽图中观察到的脯氨酸酰胺化水平与通过成像毛细管等电聚焦和pH梯度离子交换色谱法测量的碱性峰水平之间存在直接相关性。讨论了这些观察结果对治疗性抗体生产的重要性。
We report a case study of an IgG1 with a unique basic charge variant profile caused by C-terminal proline amidation on either one or two heavy chains. The proline amidation was sensitive to copper ion concentration in the production media during cell culture: the higher the Cu2+ ion concentration, the higher the level of proline amidation detected. This conclusion was supported by the analysis of samples that revealed direct correlation between the proline amidation level observed from peptide maps and the level of basic peaks measured by imaged capillary isoelectric focusing and a pH gradient ion-exchange chromatography method. The importance of these observations to therapeutic antibody production is discussed.