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Archives of Toxicology

, Volume 93, Issue 7, pp 1853–1863 | Cite as

Verification of soman-related nerve agents via detection of phosphonylated adducts from rabbit albumin in vitro and in vivo

  • Feiyan Fu
  • Runli Gao
  • Ruihua Zhang
  • Pengcheng Zhao
  • Xiaogang Lu
  • Liqin Li
  • Hongmei WangEmail author
  • Chengxin PeiEmail author
Analytical Toxicology

Abstract

A major challenge in organophosphate compound (OP) and OP nerve agent (OPNA) research has been in the identification and utilization of reliable biomarkers for rapid, sensitive, and efficient detection of OP exposure. Albumin has been widely studied as a biomarker for retrospective verification of exposure to OPNAs, including soman (GD), by detecting the phosphonylation of specific amino acid residues. The aim of the present study was to identify binding sites between GD and rabbit serum albumin in vitro and in vivo. A nano-liquid chromatography coupled with a quadrupole-orbitrap mass spectrometry (nLC-Q-Orbitrap-MS) was used to examine the GD-modified adducts of rabbit albumin. A total of 11 GD-modified sites were found in rabbit serum albumin across three experimental models. The following five GD-modified rabbit albumin sites, which were all lysine residues, were established in vivo: K188, K329, K162, K233, and K525. Two of these five lysine residues, K188 in peptide EK*ALISAAQER and K162 in peptide YK*AILTECCEAADK, were stable for at least 7 days in vivo. Molecular simulation of the GD–albumin interaction provided theoretical evidence for reactivity of the identified lysine residues. The findings suggest that these modifiable lysine residues are potential biomarkers of GD exposure for retrospective analysis by Q-Orbitrap-MS.

Keywords

Nerve agents Soman Albumin Mass spectrometry Q-orbitrap Lysine adducts 

Notes

Acknowledgements

This work was performed with the financial support of National Key R&D Program of China (Grant No. 2018YFC1602600).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

204_2019_2485_MOESM1_ESM.docx (2.2 mb)
Supplementary material 1 (DOCX 2239 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of NBC Protection for CivilianBeijingChina

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