Albumin is a new biomarker of organophosphorus compounds (OPs) and nerve agents (OPNAs) for retrospective verification. Recent studies on OPs adducts show that amino acid residues can covalently bind to OPs and OPNAs. In this article, after being incubated with soman, sarin, cyclosarin, VX, ethyl tabun, and propyl tabun, human serum albumin (HSA) is analyzed by quadrupole-Orbitrap mass spectrometer (Q Exactive LC-MS/MS). In addition to the three known phosphonylated sites, six new sites modified by OPNAs are detected. To identify the most reactive residue, we calculate the area ratio of the modified peptides to the whole peptides. The result demonstrates that tyrosine 263 (Y263) in peptide Y263ICENQDSISSK, which has been poisoned with six kinds of nerve agents, possesses the highest reactivity. The structure characteristics based on molecular simulation provide a theoretical evidence for the reactivity of the nine binding sites. It suggests that Y263 also has the potential to be used as a biomarker to detect OPNAs exposure, and the presented Q Exactive LC-MS/MS method might be of relevance for the verification of new phosphonylated sites.
Keywords: Albumin; Mass spectrometry; Nerve agents; Organophosphorus compounds; Tyrosine adducts.
Copyright © 2018. Published by Elsevier B.V.