期刊
SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-020-63078-5
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [17H03975, 16H05656, 17H05130]
- Japan Agency for Medical Research and Development (AMED) [18ae0101066h0001, 19ak0101074h1503]
- Grants-in-Aid for Scientific Research [17H05130, 16H05656, 17H03975] Funding Source: KAKEN
We oxidized histidine residues in monoclonal antibody drugs of immunoglobulin gamma 1 (IgG1) using ultraviolet C irradiation (UVC: 200-280nm), which is known to be potent for sterilization or disinfection. Among the reaction products, we identified asparagine and aspartic acid by mass spectrometry. In the photo-induced oxidation of histidine in angiotensin II, O-18 atoms from (H2O)-O-18 in the solvent were incorporated only into aspartic acid but not into asparagine. This suggests that UVC irradiation generates singlet oxygen and induces [2+2] cycloaddition to form a dioxetane involving the imidazole C-gamma-C-delta 2 bond of histidine, followed by ring-opening in the manner of further photo-induced retro [2+2] cycloaddition. This yields an equilibrium mixture of two keto-imines, which can be the precursors to aspartic acid and asparagine. The photo-oxidation appears to occur preferentially for histidine residues with lower pK(a) values in IgG1. We thus conclude that the damage due to UVC photo-oxidation of histidine residues can be avoided in acidic conditions where the imidazole ring is protonated.
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