Diisopropylfluorophosphate DFP

This key enzyme of the nervous system is inactivated irreversibly by powerful phosphorus-containing poisons that had been developed as insecticides and as war gases (nerve gases, Box 12-C). Around 1949, the nerve gas diisopropylfluorophosphate (DFP) was shown also to inactivate chymotrypsin. When radioactive 32P-containing DFP was allowed to react the 32P became... 

Dihydroxyproline 80 Diiron desaturases 863 Diiron oxygenases 863 Diiron proteins 862-864 Diiron-tyrosinate proteins 862-863 Diisopropylfluorophosphate (DFP, diisopropylphosphofluoridate) 610s Dimethylallyl diphosphate 712s Dimethylallyl pyrophosphate, condensation of 527... 

Diisopropylfluorophosphate (DFP) and phenylmethanesulfonyl fluoride (PMSF), both organophosphorus inhibitors, are potent irreversible inhibitors of serine proteases. However, because of their additional inhibition of acetylcholinesterase these compounds are highly toxic [26]. Another toxic but potent trypsin inhibitor is (4-aminophenyl)-methanesulfonyl... 

Competitive inhibition of the carboxypeptidase from A. saitoi by small substrates was found with hydrocinnamic acid, indole-3-propionic acid, and 4-phenylbutyric acid [80], The K for hydrocinnamic acid inhibition was 4 x 10 4 M. Diisopropylfluorophosphate (DFP) and tosyl-L-phenylalanylchloromethane (TPCK) were also powerful inhibitors of the carboxypeptidase from A. oryzae (80). />-Chloromercuribenzoate (PCMB) and iodoacetic acid were also powerful inhibitors of the carboxypeptidase from A. saitoi, while the inhibitors of DFP, TPCK, PCMB, and iodoacetic acid on the carboxypeptidase from A. saitoi were less than that of A. oryzae [80], As the carboxypeptidase activity of A. saitoi has no effect when used with ethylenediaminetetraacetate (EDTA) and o-phenanthroline, the enzyme is a different type of carboxypeptidase from those of the pancreatic sources, carboxypeptidase A and carboxypeptidase B [80],... 

The interactions of diisopropylfluorophosphate (DFP) with model MgO and CaO surfaces have been investigated using density functional (DFT) and Mpller-Plesset second order perturbation techniques [67]. Geometries of considered complexes were fully optimized at the DFT level. The calculated interaction energies and the corresponding thermodynamic properties show that DFP is physisorbed on these two model oxide surfaces and the adsorption on the MgO surface is stronger. 

Diisopropylfluorophosphate (DFP) is an artifically produced (nerve gas-like) compound that inhibits serine proteases and esterases. Inactive enzymes may be activated by dissociation into subunits such as is the case with cAMP-dependent protein kinases. 

Mechanism of action Isoflurophate [eye soe FLURE oh fate] (diisopropylfluorophosphate, DFP) is an organophosphate that covalently binds to a serine-OH at the active site of acetylcholinesterase (Figure 4.9). Once this occurs, the enzyme is permanently inactivated, and restoration of acetylcholinesterase activity requires the synthesis of new enzyme molecules. Following covalent modification of acetylcholinesterase, the phosphorylated enzyme slowly releases one of its isopropyl groups (Figure 4.9). The loss of an alkyl group, which is called... 

The most thoroughly investigated pancreatic lipase is from the pig. Most of our knowledge of the structure and properties of this enzyme comes from P. Desnuelle and his co-workers in Marseille (3) (Table III). The lipase occurs in two similar forms, isoenzymes Lipase A and Lipase B. There is no known proenzyme (zymogen). The enzyme does not react with diisopropylfluorophosphate (DFP), the standard inhibitor... 

The incor poration of phosphorus. Enzyme preparations from oxidized trypsinogen of varying degrees of hydrolytic activity were allowed to react with diisopropylfluorophosphate (DFP) and the amounts of incorporated phosphorus determined. Irrespective of the activity values reached after complete activation, 1 mole of phosphorus per mole (24,000 gm) of protein was incorporated. A partially activated sample, having approximately 3 % activity as compared with 25 % on maximum activation, contained only 0.17 mole of phosphorus. After complete activation this value increased to 1 mole (Table XXV). 

Proteins. Bovine insulin, a-chymotrypsin and ribonuclease were purchased from Sigma Chemical Company. Inactivated diisopropyl-phosphoryl(DIP)-a-chymotrypsin was prepared by incubation with diisopropylfluorophosphate(DFP) (25). 

CMV protease is a serine protease, and labeling with diisopropylfluorophosphate (DFP) has identified Serl32 as the active site serine (4,5). The structure of the CMV protease containing the diisopropylphosphorylserine at residue 132... 

Dube, S.N., Kumar, D., Sikder, A.K., Jaiswal, D.K., and Das Gupta, S., Therapeutic efficacy of bis-pyridinium oximes against diisopropylfluorophosphate (DFP) and soman intoxication in rodents. Pharmazie, 47,68-69,1992. 

Smallbridge RC, Carr FE and Fein HG (1991). Diisopropylfluorophosphate (DFP) reduces serum prolactin, thyrotropin, luteinizing hormone, and... 

Enzyme inhibitors are of various types. For example, we can distinguish between irreversible and reversible inhibition. Sometimes an inhibitor reacts so strongly with the active center of an enzyme that the process cannot easily be reversed. Diisopropylfluorophosphate (DFP), for example, undergoes an irreversible reaction with the active centers of certain enzymes, with the liberation of hydrogen fluoride. One of the enzymes with which it reacts is cholinesterase, which is responsible for the functioning of the nerves. As a result DFP is a very powerful nerve gas. Poisons like potassium cyanide exert their action by the irreversible inhibition of enzymes which catalyze oxidative reactions. 

Considerable advance has recently been made in the purification of bovine thrombin with the demonstration by Rasmussen (1955) that most of the active component of commercial thrombin preparations can be separated from the inactive protein impurities by chromatography on columns of Amberlite IRC-50 resin. This enzyme can be inhibited with diisopropylfluorophosphate (DFP) (Gladner and Laki, 1956 Miller and Van Vunakis, 1956) and reactivated by nucleophilic reagents such as hydroxamic acid (Gladner and Laki, 1956). On the assumption that DFP and thrombin combine in a mole ratio of 1 1 a molecular weight of 13,700 can be calculated (Gladner el al., 1958). The DFP is bound to a seryl residue, the sequence around which bears remarkable similarities to those of other enzymes which combine with DFP, as shown in Table XIII. 

Diisopropylfluorophosphate (DFP) is an organophos-phorus compound (OP) that has not been used as a pesticide, chemical warfare agent or plasticizer. However, a search of the PubMed database yielded 3,514 results searching for different s)mon5nns in titles and abstracts, as indicated in Table 57.1. 

Funke, A., Benoit, G., Jacob, J., 1955. Quaternary ammonium compounds in the hydroxamic acid series. I. Synthesis of dimethylaminobenzoylhydroxamic acid methiodides, antagonists of diisopropylfluorophosphate (DFP). C. R. Hebd. Seances Acad. Sci. 240 (26), 2575-2577. (in French). 

Grob, D., Lilienthal Jr., J.L., 1947. The administration of diisopropylfluorophosphate (DFP) to man effect on plasma and erythrocyte cholinesterase general systemic effects use in study of hepatic function and erythropoiesis and some properties of plasma cholinesterase. Bull. Johns Hopkins Hosp. 81 (4), 217-244. 

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