Rapid structural discrimination of IgG antibodies by multicharge-state collision-induced unfolding

文献类型： 外文期刊

第一作者： Yin, Zhibin

作者： Yin, Zhibin;Du, Mingyi;Chen, Dong;Zhang, Wenyang;Huang, Wenjie;Yan, Shijuan;Du, Mingyi;Chen, Dong;Wu, Xinzhou

作者机构：

期刊名称：RSC ADVANCES （ 影响因子：3.361； 五年影响因子：3.39 ）

ISSN：

年卷期： 2021 年 11 卷 58 期

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收录情况： SCI

摘要： Immunoglobulin G (IgG) antibodies are an important class of biotherapeutics that target various diseases, such as cancers, neurodegenerative disorders, and autoimmune diseases, yet rapid discrimination of IgG antibodies remains a great challenge due to heterogeneity, flexibility, and large size. Herein, we demonstrate a simplified multicharge-state collision-induced unfolding (CIU) method for rapid differentiation of four IgG isotypes that differ in terms of the numbers and patterns of disulfide bonds, bypassing tedious single charge-state selection in advance. The results presented herein reveal that gas-phase unfolding behaviors have a strong dependence on charge states outside IgG surfaces; therefore, multicharge-state CIU analysis of IgG subtypes could offer a great opportunity to gain deeper insights into their gas-phase structural differentiation. The full discrimination of IgG antibody isoforms that possess different disulfide bond numbers and even subtle disulfide bonding patterns can be achieved based on their charge-dependent gas-phase unfolding behaviors and root-mean square deviation in CIU difference spectra. Taken together, the incorporation of all charge states observed in a native ion mobility-mass spectrometry (IM-MS) experiment to CIU analysis could make this strategy sensitive to more subtle structural discrepancies, facilitating the rapid discrimination and evaluation of innovative structurally similar biotherapeutic candidates with unexplored functions.

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