PMID- 35478034 OWN - NLM STAT- MEDLINE DCOM- 20220524 LR - 20220524 IS - 1618-2650 (Electronic) IS - 1618-2642 (Linking) VI - 414 IP - 14 DP - 2022 Jun TI - A proteomics strategy for the identification of multiple sites in sulfur mustard-modified HSA and screening potential biomarkers for retrospective analysis of exposed human plasma. PG - 4179-4188 LID - 10.1007/s00216-022-04070-y [doi] AB - A major challenge for the unequivocal verification of alleged exposure to sulfur mustard (HD) lies in identifying its multiple modifications on endogenous proteins and utilizing these modified proteins to achieve accurate, sensitive, and rapid detection for retrospective analysis of HD exposure. As the most abundant protein in human plasma, human serum albumin (HSA) can react with many xenobiotics, such as HD, to protect the body from damage. The HSA adducts induced by HD have been used as biomarkers for the verification of HD exposure. In this study, the modification sites on HSA by HD were identified through application of the bottom-up strategy used in proteomics, and 41 modified sites were discovered with seven types of amino acids, of which 3 types were not previously reported. Then, different enzymes, including pepsin, endoproteinase Glu-C, and pronase, were applied to digest HD-HSA to produce adducts with hydroxyethylthioethyl (HETE) groups, which may be used as potential biomarkers for HD exposure. As candidates for retrospective analysis, sixteen adducts were obtained and characterized with ultra-high-pressure liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry (UHPLC-QE Focus MS). These potential biomarkers were evaluated in human plasma that was exposed in vitro to HD and five of its analogues. This study integrated the identification of modification sites through application of the bottom-up strategy of proteomics and screening biomarkers, providing a novel strategy for retrospective detection of the exposure of xenobiotic chemicals. CI - (c) 2022. Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Chen, Bo AU - Chen B AD - State Key Laboratory of NBC Protection for Civilian, Laboratory of Analytical Chemistry, Research Institute of Chemical Defence, Beijing, 102205, People's Republic of China. FAU - Zhang, Qiaoli AU - Zhang Q AD - State Key Laboratory of NBC Protection for Civilian, Laboratory of Analytical Chemistry, Research Institute of Chemical Defence, Beijing, 102205, People's Republic of China. FAU - Ren, Zhe AU - Ren Z AD - School of Chemistry and Chemical Engineering, Nanjing University of Sciences & Technology, Nanjing, 210094, People's Republic of China. FAU - Zhang, Tao AU - Zhang T AD - State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research, Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing, 102206, People's Republic of China. FAU - Yu, Huilan AU - Yu H AD - State Key Laboratory of NBC Protection for Civilian, Laboratory of Analytical Chemistry, Research Institute of Chemical Defence, Beijing, 102205, People's Republic of China. FAU - Liu, Changcai AU - Liu C AD - State Key Laboratory of NBC Protection for Civilian, Laboratory of Analytical Chemistry, Research Institute of Chemical Defence, Beijing, 102205, People's Republic of China. FAU - Yang, Yang AU - Yang Y AD - State Key Laboratory of NBC Protection for Civilian, Laboratory of Analytical Chemistry, Research Institute of Chemical Defence, Beijing, 102205, People's Republic of China. FAU - Xu, Ping AU - Xu P AD - State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research, Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing, 102206, People's Republic of China. xuping_bprc@126.com. FAU - Liu, Shilei AU - Liu S AD - State Key Laboratory of NBC Protection for Civilian, Laboratory of Analytical Chemistry, Research Institute of Chemical Defence, Beijing, 102205, People's Republic of China. liu_shilei@lacricd.com. LA - eng PT - Journal Article DEP - 20220427 PL - Germany TA - Anal Bioanal Chem JT - Analytical and bioanalytical chemistry JID - 101134327 RN - 0 (Biomarkers) RN - 0 (Chemical Warfare Agents) RN - T8KEC9FH9P (Mustard Gas) RN - ZIF514RVZR (Serum Albumin, Human) SB - IM MH - Biomarkers/analysis MH - *Chemical Warfare Agents/analysis MH - Humans MH - *Mustard Gas/analysis MH - Proteomics MH - Retrospective Studies MH - Serum Albumin, Human/chemistry MH - Tandem Mass Spectrometry/methods OTO - NOTNLM OT - Exposure biomarkers OT - Human serum albumin OT - Proteomics OT - Sulfur mustard EDAT- 2022/04/29 06:00 MHDA- 2022/05/25 06:00 CRDT- 2022/04/28 05:40 PHST- 2022/03/02 00:00 [received] PHST- 2022/04/06 00:00 [accepted] PHST- 2022/03/27 00:00 [revised] PHST- 2022/04/29 06:00 [pubmed] PHST- 2022/05/25 06:00 [medline] PHST- 2022/04/28 05:40 [entrez] AID - 10.1007/s00216-022-04070-y [pii] AID - 10.1007/s00216-022-04070-y [doi] PST - ppublish SO - Anal Bioanal Chem. 2022 Jun;414(14):4179-4188. doi: 10.1007/s00216-022-04070-y. Epub 2022 Apr 27.