一类新芥子气损伤生物标志物的体外高分辨质谱鉴定研究

杨展 徐斌 陈佳 吴剑峰 何跃忠 谢剑炜

引用本文: 杨展, 徐斌, 陈佳, 吴剑峰, 何跃忠, 谢剑炜. 一类新芥子气损伤生物标志物的体外高分辨质谱鉴定研究[J]. 分析化学, 2021, 49(10): 1733-1742. doi: 10.19756/j.issn.0253-3820.211256 shu
Citation:  YANG Zhan,  XU Bin,  CHEN Jia,  WU Jian-Feng,  HE Yue-Zhong,  XIE Jian-Wei. Identification of Some Novel Damage Biomarkers of Sulfur Mustard by High Resolution Mass Spectrometry in Vitro[J]. Chinese Journal of Analytical Chemistry, 2021, 49(10): 1733-1742. doi: 10.19756/j.issn.0253-3820.211256 shu

一类新芥子气损伤生物标志物的体外高分辨质谱鉴定研究

    通讯作者: 吴剑峰,E-mail:ammswjf@163.com
  • 基金项目:

    国家重点研发计划项目(Nos.2018YFC1602600,2020YFF0305000)资助。

摘要: 芥子气(SM)具有亲电性,是典型的高反应活性烷基化毒剂,人体经其暴露后,体内会生成多种水解氧化代谢产物和蛋白质、核酸加合物等,其中,二乙烯砜(Divinyl Sulfone,DVS)是近期发现的一种重要氧化代谢产物,具有类芥子气的反应活性和更高的毒性。以DVS及其谷胱甘肽(Glutathione,GSH)的二相代谢产物DVS-GSH分别染毒人血清白蛋白(HSA)与人源血浆,经蛋白酶K酶解和HLB小柱固相萃取净化后,采用UPLC-Q-Exactive Orbitrap高分辨质谱分析检测,鉴定出3种全新结构的白蛋白加合物:DVS-Cys-Pro-Phe (DVS-CPF)、Phe-Pro-Cys-DVS-Cys-Pro-Phe (FPC-DVS-CPF)和GSH-DVS-Cys-Pro-Phe (GSH-DVS-CPF)。研究结果表明,含有高反应活性烯键的DVS分子可与白蛋白的Cys-34残基发生特异性加合反应,并且其二相代谢产物DVS-GSH仍可继续发生加合反应,形成一类新的白蛋白加合物。鉴定的新结构加合物不仅为确证SM暴露和中毒诊断提供了新的损伤生物标志物,也为从新的角度阐述SM的损伤机制提供了实验证据。

English


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  • 收稿日期:  2021-03-28
  • 修回日期:  2021-06-02
通讯作者: 陈斌, bchen63@163.com
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