Binding and hydrolysis of soman by human serum albumin

Bin Li, Florian Nachon, Marie Thérèse Froment, Laurent Verdier, Jean Claude Debouzy, Bernardo Brasme, Emilie Gillon, Lawrence M Schopfer, Oksana Lockridge, Patrick Masson

Research output: Contribution to journalArticle

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Abstract

Human plasma and fatty acid free human albumin were incubated with soman at pH 8.0 and 25°C. Four methods were used to monitor the reaction of albumin with soman: progressive inhibition of the aryl acylamidase activity of albumin, the release of fluoride ion from soman, 31P NMR, and mass spectrometry. Inhibition (phosphonylation) was slow with a bimolecular rate constant of 15 ± 3 M-1 min-1. MALDI-TOF and tandem mass spectrometry of the soman-albumin adduct showed that albumin was phosphonylated on tyrosine 411. No secondary dealkylation of the adduct (aging) occurred. Covalent docking simulations and 31P NMR experiments showed that albumin has no enantiomeric preference for the four stereoisomers of soman. Spontaneous reactivation at pH 8.0 and 25°C, measured as regaining of aryl acylamidase activity and decrease of covalent adduct (pinacolyl methylphosphonylated albumin) by NMR, occurred at a rate of 0.0044 h -1, indicating that the adduct is quite stable (t1/2 = 6.5 days). At pH 7.4 and 22°C, the covalent soman-albumin adduct, measured by MALDI-TOF mass spectrometry, was more stable (t1/2 = 20 days). Though the concentration of albumin in plasma is very high (about 0.6 mM), its reactivity with soman (phosphonylation and phosphotriesterase activity) is too slow to play a major role in detoxification of the highly toxic organophosphorus compound soman. Increasing the bimolecular rate constant of albumin for organophosphates is a protein engineering challenge that could lead to a new class of bioscavengers to be used against poisoning by nerve agents. Soman-albumin adducts detected by mass spectrometry could be useful for the diagnosis of soman exposure.

Original languageEnglish (US)
Pages (from-to)421-431
Number of pages11
JournalChemical Research in Toxicology
Volume21
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint

Soman
Serum Albumin
Albumins
Hydrolysis
aryl acylamidase
Mass spectrometry
Mass Spectrometry
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Nuclear magnetic resonance
Phosphoric Triester Hydrolases
Rate constants
Organophosphorus Compounds
Dealkylation
Protein Engineering
Plasma (human)
Stereoisomerism
Organophosphates
Poisons
Detoxification
Tandem Mass Spectrometry

ASJC Scopus subject areas

  • Toxicology

Cite this

Li, B., Nachon, F., Froment, M. T., Verdier, L., Debouzy, J. C., Brasme, B., ... Masson, P. (2008). Binding and hydrolysis of soman by human serum albumin. Chemical Research in Toxicology, 21(2), 421-431. https://doi.org/10.1021/tx700339m

Binding and hydrolysis of soman by human serum albumin. / Li, Bin; Nachon, Florian; Froment, Marie Thérèse; Verdier, Laurent; Debouzy, Jean Claude; Brasme, Bernardo; Gillon, Emilie; Schopfer, Lawrence M; Lockridge, Oksana; Masson, Patrick.

In: Chemical Research in Toxicology, Vol. 21, No. 2, 01.02.2008, p. 421-431.

Research output: Contribution to journalArticle

Li, B, Nachon, F, Froment, MT, Verdier, L, Debouzy, JC, Brasme, B, Gillon, E, Schopfer, LM, Lockridge, O & Masson, P 2008, 'Binding and hydrolysis of soman by human serum albumin', Chemical Research in Toxicology, vol. 21, no. 2, pp. 421-431. https://doi.org/10.1021/tx700339m
Li B, Nachon F, Froment MT, Verdier L, Debouzy JC, Brasme B et al. Binding and hydrolysis of soman by human serum albumin. Chemical Research in Toxicology. 2008 Feb 1;21(2):421-431. https://doi.org/10.1021/tx700339m
Li, Bin ; Nachon, Florian ; Froment, Marie Thérèse ; Verdier, Laurent ; Debouzy, Jean Claude ; Brasme, Bernardo ; Gillon, Emilie ; Schopfer, Lawrence M ; Lockridge, Oksana ; Masson, Patrick. / Binding and hydrolysis of soman by human serum albumin. In: Chemical Research in Toxicology. 2008 ; Vol. 21, No. 2. pp. 421-431.
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