Detection of Histidine Oxidation in a Monoclonal Immunoglobulin Gamma (IgG) 1 Antibody

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• 作者：Masato Amano ; Naoki Kobayashi ; Masayuki Yabuta ; Susumu Uchiyama ; Kiichi Fukui
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：August 5, 2014
• 年：2014
• 卷：86
• 期：15
• 页码：7536-7543
• 全文大小：327K
• ISSN：1520-6882

文摘

Although oxidation of methionine and tryptophan are known as popular chemical modifications that occur in monoclonal antibody (mAb) molecules, oxidation of other amino acids in mAbs has not been reported to date. In this study, oxidation of the histidine residue in a human immunoglobulin gamma (IgG) 1 molecule was discovered for the first time by mass spectrometry. The oxidation of a specific histidine located at the CH₂ domain of IgG1 occurred under light stress, but it was not observed under heat stress. With the forced degradation study using several reactive oxygen species, the singlet oxygen was attributed to a reactive source of the histidine oxidation. The reaction mechanism of the histidine oxidation was proposed on the basis of the mass spectrometric analysis of IgG1 oxidized in deuterium oxide and hydrogen heavy oxide.