Citation: YANG Zhan,  LIU Yu-Long,  CHEN Jia,  WU Jian-Feng,  HE Yue-Zhong,  XIE Jian-Wei. Development of a New Synthetic Route of Tripeptide-adduct of Sulfur Mustard Exposure and Application in Confirmatory Analysis[J]. Chinese Journal of Analytical Chemistry, ;2022, 50(1): 136-144. doi: 10.19756/j.issn.0253-3820.210454 shu

Development of a New Synthetic Route of Tripeptide-adduct of Sulfur Mustard Exposure and Application in Confirmatory Analysis

  • Corresponding author: WU Jian-Feng, ammswjf@163.com
  • Received Date: 21 April 2021
    Revised Date: 16 October 2021

    Fund Project: Supported by the National Key Research and Development Program of China (Nos.2018YFC1602600, 2020YFF0305000).

  • Sulfurmustard (SM) is a typical representative of highly-toxic chemical warfare agent that is difficult to be prevented and treated. SM could produce various biomarkers with protein, glutathione and DNA, etc, besides oxidative and hydrolytic metabolism. The tripeptide-adduct hydroxyethylthioethyl-Cys-Pro-Pro (HETE-CPF) originating from Cys-34 on the human serum albumin (HSA) is a very important retrospective biomarker, which is usually used to identify SM exposure due to its long half-life and good stability. In this work, a novel synthetic route of HETE-CPF was developed with chloroethanol as the starting material. Compared with the original synthetic route using 2-chloroethyl mercaptoethanol as the starting material, the new synthetic method had less side reactions, higher yield and easier purification. Furthermore, a highly sensitive analysis method for HETE-CPF in whole blood samples was established, and the detection sensitivity was up to 2 ng/mL, which was enough to identify human plasma sample after exposure to SM. Meanwhile, it was also identified that after SM exposure via caudal vein in rats, the exposure biomarkers formed with plasma albumin were significantly different from those of human plasma, which was HETE-Cys-Pro-Tyr (HETE-CPY), not HETE-CPF. The fundamental reason might be due to their different primary sequence of albumin.
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