ISSN:
1471-4159
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Abstract: 2-Octyl-4H-1,3,2-benzodioxaphosphorin 2-oxide (octyl-BDPO) is one of the most potent inhibitors known for neuropathy target esterase (NTE) of hen brain with 50% inhibition at 0.2 nM. Two NTE-like proteins, i.e., resistant to paraoxon and sensitive to mipafox, of ∼155 and ∼119 kDa (designated NTE-155 and NTE-119, respectively) are labeled by [octyl-3H]octyl-BDPO and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Labeling with [aryl-3H]octyl-BDPO is only ∼15% of that with [octyl-3H]octyl-BDPO, indicating that the majority of the phosphorylated NTE undergoes aging with only a small proportion of nonaged target or intramolecular group transfer (“alkylation”). NTE-155 and NTE-119 have the same kinetic constants and maximal number of phosphorylation sites, equivalent for each of them to 26 fmol/mg of protein and totalling at least 0.44–1.2 µg of NTE protein/g of brain. Structure-activity investigations involving 17 combinations of organophosphorus (OP) compounds of varied chemical type, stereo-chemistry, and concentration establish an excellent correlation (r = 0.95) between inhibition of NTE activity and protein labeling and thereby the toxicological relevance of these assays, which equally implicate NTE-155 and NTE-119 (probably an autolysis product of NTE-155) as targets in OP-induced delayed neuropathy. [octyl-3H]-Octyl-BDPO is an improved probe for NTE in terms of its potency, reactivity, selectivity, and the formation of 3H-labeled NTE with a stable phosphorus-carbon bond.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1046/j.1471-4159.1995.64041680.x
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