Diisopropylfluorophosphate

Diisopropylfluorophosphate (DIFP) reacts with active-site serine ... 

Dumas DP, IR Wild, FM Raushel (1989) Diisopropylfluorophosphate hydrolysis by an organophosphate anhydrase from Pseudomonas diminuta. Biotechnol Appl Biochem 11 235-243. 

Costa LG, Murphy SD. 1986. Cholinergic and opiate involvement in the antinociceptive effect of diisopropylfluorophosphate. Pharmacol Biochem Behav 24 733-736. 

AFFINITY ABELING ACTIVE-SITE TITRATION ACETYLCHOLINESTERASE AFFINITY ABELING DIISOPROPYLFLUOROPHOSPHATE ACTIVE TRANSPORT ION PUMPS... 

The general structure of organophosphates. The X is a good leaving group. In the prototype compound DIFP, diisopropylfluorophosphate, F was used. 

Plasmin is a serine proteinase (inhibited by diisopropylfluorophosphate, phenylmethyl sulphonyl fluoride and trypsin inhibitor) with a high specificity for peptide bonds to which lysine or arginine supplies the carboxyl group. Its molecular weight is about 81 Da and its structure contains five intramolecular disulphide-linked loops (kringles) which are essential for its activity. 

FIGURE 6-16 Irreversible inhibition. Reaction of chymotrypsin with diisopropylfluorophosphate (DIFP) irreversibly inhibits the enzyme. This has led to the conclusion that Ser195 is the key active-site Ser residue in chymotrypsin. 

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... 

Iodoacetic acid, A-bromosuccinimide, and H202 were found to be strongly inhibitory, whereas iodoacetamide was only slightly inhibitory and diisopropylfluorophosphate was not inhibitory. These results suggest that tryptophan, methionine, and/or histidine, but not serine, are involved in the enzymic activity (43). 

Diisopropylfluorophosphate, in contrast to its action on other serine hydrolases, has only a slight inhibitory effect on alkaline phosphatase in the range 1-10 ml (76, 113). 

One way to test a scheme like that shown in figure 8.11 is to investigate the effects of modifying the amino acid residues that play important roles. The inhibitory effect of the reaction of Ser 195 with diisopropylfluorophosphate was mentioned earlier (also see fig. 7.18). To examine the importance of His 57, this residue can be modified by meth-... 

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... 

Carboxypeptidase P Dipeptidyl peptidase TV Enterostatin, EDTA Diisopropylfluorophosphate, IV-peptidyl- O-acylhydroxyl-amines, boronic acid analogues of proline and alanine,... 

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],... 

An irreversible inhibitor binds tightly, often covalently, to amino acid residues at the active site of the enzyme, permanently inactivating the enzyme. Examples of irreversible inhibitors are diisopropylfluorophosphate (DIPF), iodoacetamide and penicillin. 

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. 

W. Kolodziejczyk et al., Probing the role of P=0 stretching mode enhancement in nerve-agent sensors Simulation of the adsorption of diisopropylfluorophosphate on the model MgO and CaO surfaces. Chem. Phys. Lett. 450, 138-143 (2007)... 

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. 

The activation of BSSL is specific to primary bile salts. Bile salts, secondary as well as primary, protect BSSL against inactivation by intestinal proteinases. BSSL is inactivated by heating at 50°C for 1 h, but sodium taurocholate prevents loss of activity. The enzyme is stable in buffer for 1 h at 37°C between pH 3.5 and 9. It is inhibited by blood serum, 1M NaCl, protamine sulphate, eserine and diisopropylfluorophosphate (Hernell, 1975 Blackberg and Hernell, 1983). 

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... 

Diisopropylfluorophosphate] (organophosp hate) Synthetic insecticide AChE (forms phosphoryl ester with active site Serine)... 

A second type of active site selective reagent is when there is a pseudosubstrate, such as diisopropylfluorophosphate. Acting... 

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