Soman binding

Little is known about the rate of OP binding to tyrosine because the recognition of this OP binding motif is new with the writing of this chapter. Soman binding to Tyr 411 in human albumin has been measured and has been found to be slow with a bimolecular rate constant of 15 3 min (Li et al., 2008a). We expect that other proteins will be identified whose rate of OP binding to tyrosine will be fast. 

Glikson, M., Arad-Yellin, R., Ghozi, M., Raveh, L., Green, B.S., Eshhar, Z. (1992). Characterization of soman-binding antibodies raised against soman analogs. Mol. Immunol. 29 903-10. 

Black et al. (1999) found that sarin and soman bind to a tyrosine residue in human plasma and suggested that this could form the basis of a biomarker of exposure to these agents. 

Lee MS, Gippert, GP, Soman KV, Case DA, Wright PE (1989) Three-dimensional solution structure of a single zinc finger DNA-binding domain. Science 245 635... 

Soman is an irreversible inhibitor of acetylcholinesterase. Unlike the case with some acetylcholinesterase inhibitors, recovery from sublethal poisoning by Soman requires enzyme resynthesis, rather than reversible binding to the enzyme. 

Sarin and soman have been shown to bind to a tyrosine residue present in a blood protein (51). The precise site of this residue has not yet been confirmed but it is associated with the albumin fraction. An LC/ESI/MS/MS (triple quadrupole) method was developed for its detection after digestion of the albumin fraction with Pronase and clean up on a C18 SPE (solid-phase extraction) cartridge. A... 

Grigoryan, H., Schopfer, L.M., Thompson, C.M., Terry, A.V., Masson, P., Lockridge, O. (2008). Mass spectrometry identifies covalent binding of soman, sarin, chlorpyrifos oxon, diisopropyl fluorophosphate, and FP-biotin to tyrosines on tubulin a potential mechanism of long term toxicity by organophos-phoms agents. Chem. Biol. Interact. April 22. (Epub ahead of print)... 

It was shown that tabun, sarin, soman, and VX bind to the muscarinic receptor subtype m2, leading to the assumption... 

In addition, due to the reversibility of the binding reaction of sarin and soman to CarbE, it appears that CarbEs are involved in metabolic detoxification of these agents to their corresponding nontoxic metabolites isopropyl methylphosphonic acid (IMPA) and pinacolyl methylphosphonic acid (PMPA) (Jokanovic et al, 1996). 

While the biological role of ChE is presently unelear, it is known that soman, sarin, tabun, and VX bind to ChE, without any apparent toxic effects, decreasing the amount of free agents available for inhibition of AChE in the eentral nervous system and erythrocytes. Pretreatment with human... 

Li et al. (2008) have shown that soman covalently binds to albumin at tyrosine 411. The adduct is stable (/i/2 = 20 days). However, though the concentration of albumin in plasma is very high, its reactivity with soman is too slow to play a major role in detoxification of the agent. The authors concluded that soman-albumin adducts could be usefid for the diagnosis of soman exposure. Tarhoni et al. (2008) also found that OP pesticides covalently bind to albumin and that the adduct is stable for more than 7 days. 

These examples show that OPs can bind covalently to albumin under physiological conditions, and that the resultant adducts are relatively stable. OP-albumin adducts could therefore be useful as biomarkers of OP exposure. In addition, unlike cholinesterases, the soman-albumin conjugate does not age (Li et al, 2008a), making it possible to discriminate between sarin and soman exposure. OP-albumin adducts have not yet been reported in humans exposed to OPs. 

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