کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2600086 | 1562640 | 2010 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chromatographic preparation and kinetic analysis of interactions between tabun enantiomers and acetylcholinesterase
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
The easy accessibility to highly toxic OP (organophosphorus)-type chemical warfare agents (nerve agents) underlines the necessity for an effective medical treatment. Acute OP toxicity is primarily caused by inhibition of acetylcholinesterase (AChE, EC 3.1.1.7). Reactivators (oximes) of inhibited AChE are a mainstay of treatment. However, the commercially available compounds, obidoxime and pralidoxime, are considered rather ineffective against various nerve agents, including tabun. OP-type chemical warfare agents include an asymmetrical P-atom and consist of at least two stereoisomers. Previous studies with the nerve agents sarin and soman showed marked differences between (â)- and (+)-P isomers regarding AChE inhibition and stability in biological matrices. Hence, stereoselectivity is a key parameter for the development of optimized treatment. In the present study, the tabun enantiomers were isolated by semi-preparative liquid-chromatography (LC) with offline analysis by GC-PCI-MS and final characterization of optical purity (99.98% (â)-tabun and 99.83% (+)-tabun) and specific optical rotation. The inhibition and reactivation kinetics of the tabun enantiomers were determined with human and swine AChE and the aging kinetics with human AChE. The results show a large difference in the inhibitory potency between (â)- and (+)-tabun. The determination of reactivation and aging kinetics indicates that both reactions are at least in part determined by the residual (â)-tabun contamination (0.17%) of the (+)-tabun preparation. These data provide further insight into the kinetic interactions between tabun enantiomers and AChE and may contribute to the development of more effective treatment options.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 195, Issues 2â3, 2 June 2010, Pages 142-146
Journal: Toxicology Letters - Volume 195, Issues 2â3, 2 June 2010, Pages 142-146
نویسندگان
O. Tenberken, H. Thiermann, F. Worek, G. Reiter,