Progressive expansion of albumin adducts for organophosphorus nerve agent traceability based on single and group adduct collection.
A collection of OPNAs–albumin adducts
Chemical forensics
OPNAs–HSA adduct group
Organophosphorus nerve agents
Protein adducts
Journal
Analytical and bioanalytical chemistry
ISSN: 1618-2650
Titre abrégé: Anal Bioanal Chem
Pays: Germany
ID NLM: 101134327
Informations de publication
Date de publication:
03 May 2024
03 May 2024
Historique:
received:
04
03
2024
accepted:
15
04
2024
revised:
11
04
2024
medline:
3
5
2024
pubmed:
3
5
2024
entrez:
2
5
2024
Statut:
aheadofprint
Résumé
Protein adducts are important biological targets for traceability of organophosphorus nerve agents (OPNAs). Currently, the recognized biomarkers that can be used in actual samples in the field of chemical forensics only include Y411 in albumin and the active nonapeptide in butyrylcholinesterase (BChE). To explore stable and reliable protein adducts and increase the accuracy of OPNAs traceability further, we gradually expanded OPNAs-albumin adducts based on single and group adduct collection. Several stable peptides were found via LC-MS/MS analysis in human serum albumin (HSA) exposed to OPNAs in a large exposure range. These adducts were present in HSA samples exposed to OPNAs of each concentration, which provided data support for the reliability and stability of using adducts to trace OPNAs. Meanwhile, the formation mechanism of OPNAs-cysteine adduct was clarified via computer simulations. Then, these active sites found and modified peptides were used as raw materials for progressive expansion of albumin adducts. We constructed an OPNAs-HSA adducts group, in which a specific agent is the exposure source, and three or more active peptides constitute data sets for OPNAs traceability. Compared with single or scattered protein adducts, the OPNAs-HSA adduct group improves OPNAs identification by mutual verification using active peptides or by narrowing the identity range of the exposure source. We also determined the minimum detectable concentration of OPNAs for the adduct group. Two or more peptides can be detected when there is an exposure of 50 times the molar excess of OPNAs in relation to HSA. This improved the accuracy of OPNAs exposure and identity confirmation. A collection of OPNAs-albumin adducts was also examined. The collection was established by collecting, classifying, and integrating the existing albumin adducts according to the species to which each albumin belongs, the types of agents, and protease. This method can serve as a reference for discovering new albumin adducts, characteristic phosphonylated peptides, and potential biomarkers. In addition, to avoid a false negative for OPNAs traceability using albumin adducts, we explored OPNAs-cholinesterase adducts because cholinesterase is more reactive with OPNAs than albumin. Seven active peptides in red blood cell acetylcholinesterase (RBC AChE) and serum BChE can assist in OPNAs exposure and identity confirmation.
Identifiants
pubmed: 38698257
doi: 10.1007/s00216-024-05311-y
pii: 10.1007/s00216-024-05311-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
Références
Greathouse B, Zahra F, Brady MF. Acetylcholinesterase Inhibitors Toxicity. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Farah Zahra declares no relevant financial relationships with ineligible companies. Disclosure: Mark Brady declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC. 2024.
Wiercinski A, Jackson JP. Nerve Agents. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Jeremy Jackson declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023.
Sejvar JJ. Neurochemical and Neurobiological Weapons. Neurol Clin. 2020;38(4):881–96. https://doi.org/10.1016/j.ncl.2020.07.007 .
doi: 10.1016/j.ncl.2020.07.007
pubmed: 33040867
Ham Sembiring M, Nursanti O, Aisyah Rahmania T. Molecular docking and toxicity studies of nerve agents against acetylcholinesterase (AChE). J Recept Signal Transduct Res. 2024;1-8. https://doi.org/10.1080/10799893.2023.2298899 .
Robb EL, Baker MB. Organophosphate Toxicity. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Mari Baker declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC. 2023.
Hayoun MA, Smith ME, Ausman C, Yarrarapu SNS, Swoboda HD. Toxicology, V-Series Nerve Agents. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Matthew Smith declares no relevant financial relationships with ineligible companies. Disclosure: Chelsea Ausman declares no relevant financial relationships with ineligible companies. Disclosure: Siva Naga Yarrarapu declares no relevant financial relationships with ineligible companies. Disclosure: Henry Swoboda declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC. 2023.
Fu F, Liu H, Gao R, Zhao P, Lu X, Zhang R, et al. Protein adduct binding properties of tabun-subtype nerve agents after exposure in vitro and in vivo. Toxicol Lett. 2020;321:1–11. https://doi.org/10.1016/j.toxlet.2019.12.014 .
doi: 10.1016/j.toxlet.2019.12.014
pubmed: 31846690
John H, Lindl T, Reuter H, Schmeisser W, Schrader M, Thiermann H. Phosphonylated tyrosine and lysine residues as biomarkers of local exposure of human hair to the organophosphorus nerve agents sarin and VX. Drug Test Anal. 2023;15:730–44. https://doi.org/10.1002/dta.3459 .
doi: 10.1002/dta.3459
pubmed: 36787649
Liu CC, Liang LH, Yan L, Chen B, Liu XJ, Yang Y, et al. Generic detection of organophosphorus nerve agent adducts to butyrylcholinesterase in plasma using liquid chromatography-tandem mass spectrometry combined with an improved procainamide-gel separation and pepsin digestion method. J Chromatogr A. 2023;1697:463990. https://doi.org/10.1016/j.chroma.2023.463990 .
doi: 10.1016/j.chroma.2023.463990
pubmed: 37075496
McGuire JR, Bester SM, Guelta MA, Cheung J, Langley C, Winemiller MD, et al. Structural and Biochemical Insights into the Inhibition of Human Acetylcholinesterase by G-Series Nerve Agents and Subsequent Reactivation by HI-6. Chem Res Toxicol. 2021;34(3):804–16. https://doi.org/10.1021/acs.chemrestox.0c00406 .
doi: 10.1021/acs.chemrestox.0c00406
pubmed: 33538594
John H, Richter A, Siegert M, Eyer F, Thiermann H. Evidence of exposure to organophosphorus toxicants by detection of the propionylated butyrylcholinesterase-derived nonapeptide-adduct as a novel biomarker. Forensic Sci Int. 2021;323:110818. https://doi.org/10.1016/j.forsciint.2021.110818 .
doi: 10.1016/j.forsciint.2021.110818
pubmed: 33990018
John H, Thiermann H. Poisoning by organophosphorus nerve agents and pesticides: An overview of the principle strategies and current progress of mass spectrometry-based procedures for verification. J Mass Spectrom Adv Clin Lab. 2021;19:20–31. https://doi.org/10.1016/j.jmsacl.2021.01.002 .
doi: 10.1016/j.jmsacl.2021.01.002
pubmed: 34820662
pmcid: 8601002
Jiang W, Dubrovskii YA, Podolskaya EP, Murashko EA, Babakov V, Nachon F, et al. PHOS-Select Iron Affinity Beads Enrich Peptides for the Detection of Organophosphorus Adducts on Albumin. Chem Res Toxicol. 2013;26(12):1917–25. https://doi.org/10.1021/tx400352h .
doi: 10.1021/tx400352h
pubmed: 24187955
Chen S, Zhang J, Lumley L, Cashman JR. Immunodetection of serum albumin adducts as biomarkers for organophosphorus exposure. J Pharmacol Exp Ther. 2013;344(2):531–41. https://doi.org/10.1124/jpet.112.201368 .
doi: 10.1124/jpet.112.201368
pubmed: 23192655
pmcid: 3558817
Golime R, Chandra B, Palit M, Dubey DK. Adductomics: a promising tool for the verification of chemical warfare agents’ exposures in biological samples. Arch Toxicol. 2019;93(6):1473–84. https://doi.org/10.1007/s00204-019-02435-4 .
doi: 10.1007/s00204-019-02435-4
pubmed: 30923868
Goncharov NV, Belinskaia DA, Shmurak VI, Terpilowski MA, Jenkins RO, Avdonin PV. Serum Albumin Binding and Esterase Activity: Mechanistic Interactions with Organophosphates. Molecules. 2017;22(7):1201. https://doi.org/10.3390/molecules22071201 .
doi: 10.3390/molecules22071201
pubmed: 28718803
pmcid: 6151986
Fu F, Liu H, Lu X, Zhang R, Li L, Gao R, et al. Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure. Rapid Commun Mass Spectrom. 2020;34(9):e8721. https://doi.org/10.1002/rcm.8721 .
doi: 10.1002/rcm.8721
pubmed: 31899842
Lv Q, Yu HL, Yang Y, Meng FH, Dai XD, Jiang PY, et al. Screening of monoclonal antibodies against specific phosphonylation sites and analysis of serum samples exposed to soman and VX using an indirect competitive enzyme-linked immunosorbent assay. Anal Bioanal Chem. 2022;414(8):2713–24. https://doi.org/10.1007/s00216-022-03914-x .
doi: 10.1007/s00216-022-03914-x
pubmed: 35083511
Fu F, Gao R, Zhang R, Zhao P, Lu X, Li L, et al. Verification of soman-related nerve agents via detection of phosphonylated adducts from rabbit albumin in vitro and in vivo. Archives of Toxicology. 2019;93(7):1853–63. https://doi.org/10.1007/s00204-019-02485-8 .
doi: 10.1007/s00204-019-02485-8
pubmed: 31161358
Kranawetvogl T, Kranawetvogl A, Scheidegger L, Wille T, Steinritz D, Worek F, et al. Evidence of nerve agent VX exposure in rat plasma by detection of albumin-adducts in vitro and in vivo. Arch Toxicol. 2023;97(7):1873–85. https://doi.org/10.1007/s00204-023-03521-4 .
doi: 10.1007/s00204-023-03521-4
pubmed: 37264164
pmcid: 10256656
Wang J, Sun F, Lu X, Gao R, Pei C, Wang H. Retrospective detection for V-type OPNAs exposure via phosphonylation and disulfide adducts in albumin. Sci Rep. 2022;12(1):10979. https://doi.org/10.1038/s41598-022-15198-3 .
doi: 10.1038/s41598-022-15198-3
pubmed: 35768567
pmcid: 9243071
Baygildiev T, Vokuev MF, Braun AV, Yashkir VA, Rybalchenko IV, Rodin IA. Identification of 2-(diethylamino)ethylthiol dipeptide (Cys-Pro) adduct as biomarker of nerve agents VR and CVX in human plasma using liquid chromatography-high-resolution tandem mass spectrometry. Anal Bioanal Chem. 2021;413(7):1905–16. https://doi.org/10.1007/s00216-021-03158-1 .
doi: 10.1007/s00216-021-03158-1
pubmed: 33479815
Fu F, Chen J, Zhao P, Lu X, Gao R, Chen D, et al. Tracing and attribution of V-type nerve agents in human exposure by strategy of assessing the phosphonylated and disulfide adducts on ceruloplasmin. Toxicology. 2020;430:152346. https://doi.org/10.1016/j.tox.2019.152346 .
doi: 10.1016/j.tox.2019.152346
pubmed: 31857189
Bao Y, Liu Q, Chen J, Lin Y, Wu B, Xie J. Quantification of nerve agent adducts with albumin in rat plasma using liquid chromatography-isotope dilution tandem mass spectrometry. J Chromatogr A. 2012;1229:164–71. https://doi.org/10.1016/j.chroma.2012.01.032 .
doi: 10.1016/j.chroma.2012.01.032
pubmed: 22305360
Sun F, Ding J, Lu X, Gao R, Lu X, Shi E, et al. Mass spectral characterization of tabun-labeled lysine biomarkers in albumin. J Chromatogr B Analyt Technol Biomed Life Sci. 2017;1057:54–61. https://doi.org/10.1016/j.jchromb.2017.04.047 .
doi: 10.1016/j.jchromb.2017.04.047
pubmed: 28500932
Carol-Visser J, van der Schans M, Fidder A, Hulst AG, van Baar BLM, Irth H, et al. Development of an automated on-line pepsin digestion–liquid chromatography–tandem mass spectrometry configuration for the rapid analysis of protein adducts of chemical warfare agents. J Chromatography B. 2008;870(1):91–7. https://doi.org/10.1016/j.jchromb.2008.06.008 .
doi: 10.1016/j.jchromb.2008.06.008
Baygildiev capital Te CEMC, Vokuev MF, Braun AV, Yashkir VA, Rsmall u CIV, Rodin IA. Identification of 2-(diethylamino)ethylthiol dipeptide (Cys-Pro) adduct as biomarker of nerve agents VR and CVX in human plasma using liquid chromatography-high-resolution tandem mass spectrometry. Anal Bioanal Chem. 2021;413(7):1905-16. https://doi.org/10.1007/s00216-021-03158-1 .
Kranawetvogl A, Kuppers J, Siegert M, Gutschow M, Worek F, Thiermann H, et al. Bioanalytical verification of V-type nerve agent exposure: simultaneous detection of phosphonylated tyrosines and cysteine-containing disulfide-adducts derived from human albumin. Anal Bioanal Chem. 2018;410(5):1463–74. https://doi.org/10.1007/s00216-017-0787-7 .
doi: 10.1007/s00216-017-0787-7
pubmed: 29322229
Crow BS, Pantazides BG, Quinones-Gonzalez J, Garton JW, Carter MD, Perez JW, et al. Simultaneous measurement of tabun, sarin, soman, cyclosarin, VR, VX, and VM adducts to tyrosine in blood products by isotope dilution UHPLC-MS/MS. Anal Chem. 2014;86(20):10397–405. https://doi.org/10.1021/ac502886c .
doi: 10.1021/ac502886c
pubmed: 25286390
pmcid: 4515749
Fu F, Sun F, Lu X, Song T, Ding J, Gao R, et al. A Novel Potential Biomarker on Y263 Site in Human Serum Albumin Poisoned by Six Nerve Agents. J Chromatograph B. 2019;1104:168–75. https://doi.org/10.1016/j.jchromb.2018.11.011 .
doi: 10.1016/j.jchromb.2018.11.011
Onder S, Schopfer LM, Cashman JR, Tacal O, Johnson RC, Blake TA, et al. Use of Hupresin To Capture Red Blood Cell Acetylcholinesterase for Detection of Soman Exposure. Anal Chem. 2017;90(1):974–9. https://doi.org/10.1021/acs.analchem.7b04160 .
doi: 10.1021/acs.analchem.7b04160
pubmed: 29172437
pmcid: 5757501
Dafferner AJ, Schopfer LM, Xiao G, Cashman JR, Yerramalla U, Johnson RC, et al. Immunopurification of Acetylcholinesterase from Red Blood Cells for Detection of Nerve Agent Exposure. Chem Res Toxicol. 2017;30(10):1897–910. https://doi.org/10.1021/acs.chemrestox.7b00209 .
doi: 10.1021/acs.chemrestox.7b00209
pubmed: 28892361
pmcid: 5646370
Li B, Schopfer LM, Hinrichs SH, Masson P, Lockridge O. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay for organophosphorus toxicants bound to human albumin at Tyr411. Anal Biochem. 2007;361(2):263–72. https://doi.org/10.1016/j.ab.2006.11.018 .
doi: 10.1016/j.ab.2006.11.018
pubmed: 17188226
Worek F, Thiermann H, Koller M, Wille T. In Vitro Interaction of Organophosphono- and Organophosphorothioates with Human Acetylcholinesterase. Molecules. 2020;25(13):3029. https://doi.org/10.3390/molecules25133029 .
doi: 10.3390/molecules25133029
pubmed: 32630769
pmcid: 7412149
John H, Breyer F, Thumfart JO, Hochstetter H, Thiermann H. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for detection and identification of albumin phosphylation by organophosphorus pesticides and G- and V-type nerve agents. Anal Bioanal Chem. 2010;398(6):2677–91. https://doi.org/10.1007/s00216-010-4076-y .
doi: 10.1007/s00216-010-4076-y
pubmed: 20730528
Schopfer LM, Lockridge O. Analytical approaches for monitoring exposure to organophosphorus and carbamate agents through analysis of protein adducts. Drug Test Anal. 2012;4(3–4):246–61. https://doi.org/10.1002/dta.1325 .
doi: 10.1002/dta.1325
pubmed: 22359362
Williams NH, Harrison JM, Read RW, Black RM. Phosphylated tyrosine in albumin as a biomarker of exposure to organophosphorus nerve agents. Arch Toxicol. 2007;81(9):627–39. https://doi.org/10.1007/s00204-007-0191-8 .
doi: 10.1007/s00204-007-0191-8
pubmed: 17345062
Kranawetvogl A, Kuppers J, Gutschow M, Worek F, Thiermann H, Elsinghorst PW, et al. Identification of novel disulfide adducts between the thiol containing leaving group of the nerve agent VX and cysteine containing tripeptides derived from human serum albumin. Drug Test Anal. 2017;9(8):1192–203. https://doi.org/10.1002/dta.2144 .
doi: 10.1002/dta.2144
pubmed: 27935238
Kranawetvogl A, Worek F, Thiermann H, John H. Modification of human serum albumin by the nerve agent VX: microbore liquid chromatography/electrospray ionization high-resolution time-of-flight tandem mass spectrometry method for detection of phosphonylated tyrosine and novel cysteine containing disulfide adducts. Rapid Commun Mass Spectrom. 2016;30(19):2191–200. https://doi.org/10.1002/rcm.7707 .
doi: 10.1002/rcm.7707
pubmed: 27490696
Saeidian H, Mirkhani V, Faraz SM, Naseri MT, Babri M. Characterization of Isomeric VX Nerve Agent Adducts on Albumin in Human Plasma Using Liquid Chromatography-Tandem Mass Spectrometry. Eur J Mass Spectrom. 2015;21(6):783–9. https://doi.org/10.1255/ejms.1400 .
doi: 10.1255/ejms.1400