Binding and Hydrolysis of Soman by Human Serum Albumin

• DOI: 10.1021/tx700339m
• Publication Date: 2007-12-29T06:00:46Z
• Authors: Bin Li; Florian Nachon; Marie-Thérèse Fro...; Laurent Verdier; Jean-Claude Debouzy; Bernardo Brasme; Emilie Gillon; Lawrence M. Schopfer; Oksana Lockridge; Patrick Masson
• Keywords: Serum Albumin

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