Diisopropyl fluorophosphate agent

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)... 

The clinically useful anticholinesterase agents diisopropyl fluorophosphate (DFP, Floropryl) and echothiophate iodide (Phospholine Iodide [PI]) demonstrate an indirect-acting mechanism resulting in increased levels of acetylcholine at the cholinergic receptor sites. The inhibition of acetylcholinesterase produces a relatively long-lasting and irreversible effect of maintaining active levels of acetylcholine at the parasympathetic synapses. 

Fluorophosphates are also highly toxic and relatively volatile. Sarin and soman are chemical warfare agents. Diisopropyl fluorophosphate (DFP) is often used by biochemists to study serine-active enzymes. Mipafox and DFP cause OPIDN in humans and experimental animals. 

Nerve agents also react with a tyrosine residue associated with the albumin fraction in blood (Black et al, 1999) (Figure 10). Analysis of tryptic digests from plasma incubated with sarin identified a phosphylated tripeptide, MeP(0)(0 Pr)-Tyr-Thr-Lys, consistent with the protein being albumin (tyrosine residue 411), although this sequence is common and occurs in other proteins. Before the advent of modern mass spectrometry, diisopropyl fluorophosphate was reported to... 

In a similar series of experiments, our laboratory demonstrated that topical exposure to a nerve agent stimulant, diisopropyl fluorophosphate (DFP), more than doubled permethrin absorption (Baynes etal., 2002). This significant effect on... 

Because of its high concentration in human plasma, BChE is also used as a biomarker for detection of exposure to OP pesticides and nerve agents. Hence, the sensor was likewise evaluated for detection of BChE-OP biomarkers. The detection method is the same as the protocol described previously in section 4.1 however, the chemical nerve agent (stracturally similar to Sarin) diisopropyl fluorophosphate (DFP) was chosen as a model OP in this studies. 

The diisopropylfluorophosphatase (DFPase) is found in cephalopod nerve, hepatopancreas and saliva from squid (Anderson et al. 1988). Structurally similar to PONl, the DFPase also is a calcium-containing hydrolase with a six-bladed p-propeUer fold and readily hydrolysis the organophosphate fluoride, diisopropyl-fluorophosphate (DFP), as well as the nerve agents sarin, soman and cyclosarin, in addition to the cyanide-containing OP, the nerve agent tabun (Fig. 3.15). DFPase was initially found to hydrolyze P-F and P-CN bonds and to be inert toward P-0 or P-S bonds (Bigley and Raushel 2013). 

There have been descriptions of the acute effects in humans that follow high-dose exposure (>LDso) to nerve agents soman, sarin, and VX (Inoue, 1995 Nozaki et al., 1995 Nakajima et al., 1997). The similar cluster of behavioral symptoms (anxiety, psychomotor depression, intellectual impairment, and sleep disturbance) was observed in the immediate period after resolution of the acute signs of intoxication and then slowly faded with time, somehmes taking months to be fully resolved. The CNS symptoms noted after short-term exposure of humans to diisopropyl fluorophosphate (DFP) were... 

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