Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure
Annual rept. 1 Apr 2008-31 Mar 2009
NEBRASKA UNIV MEDICAL CENTER OMAHA
Pagination or Media Count:
Organophosphorus esters OP are known to make a covalent bond with the active site serine in the consensus sequence GXSXG of esterases and proteases. However, the site of attachment to proteins that have no active site serine has only recently been recognized as tyrosine. In last years report we provided mass spectrometry evidence that soman, sarin, DFP, chlorpyrifos oxon, dichlorvos, and FP-biotin bound to tyrosine in 3 proteins. We now report binding of organophosphorus agents to tyrosinein 12 proteins. This suggests that diagnosis of exposure to OP may become possible by monitoring adducts on tyrosine, for example in albumin. The advantages of using organophosphorus-labeled albumin as a biomarker of exposure are that the albumin adduct is stable, and the OPalbumin adduct does not age. The soman adduct on plasma butyrylcholinesterase was used to determine the limit of detection of soman exposure ex vivo. A concentration of soman that inhibited butyrylcholinesterase in human plasma 2 was detectable in the multiple reaction monitoring mode of the mass spectrometer.
- Medicine and Medical Research
- Organic Chemistry
- Chemical, Biological and Radiological Warfare