6711-89-3Relevant academic research and scientific papers
Reversal of Tabun Toxicity Enabled by a Triazole-Annulated Oxime Library—Reactivators of Acetylcholinesterase
Kovarik, Zrinka,Kalisiak, Jaros?aw,Hrvat, Nikolina Ma?ek,Katalini?, Maja,Zorbaz, Tamara,?unec, Suzana,Green, Carol,Radi?, Zoran,Fokin, Valery V.,Sharpless, K. Barry,Taylor, Palmer
supporting information, p. 4100 - 4114 (2019/02/20)
Acetylcholinesterase (AChE), an enzyme that degrades the neurotransmitter acetylcholine, when covalently inhibited by organophosphorus compounds (OPs), such as nerve agents and pesticides, can be reactivated by oximes. However, tabun remains among the most dangerous nerve agents due to the low reactivation efficacy of standard pyridinium aldoxime antidotes. Therefore, finding an optimal reactivator for prophylaxis against tabun toxicity and for post-exposure treatment is a continued challenge. In this study, we analyzed the reactivation potency of 111 novel nucleophilic oximes mostly synthesized using the CuAAC triazole ligation between alkyne and azide building blocks. We identified several oximes with significantly improved in vitro reactivating potential for tabun-inhibited human AChE, and in vivo antidotal efficacies in tabun-exposed mice. Our findings offer a significantly improved platform for further development of antidotes and scavengers directed against tabun and related phosphoramidate exposures, such as the Novichok compounds.
In vitro visualization of betaine aldehyde synthesis and oxidation using hyperpolarized magnetic resonance spectroscopy
Allouche-Arnon, Hyla,Gamliel, Ayelet,Sosna, Jacob,Gomori, J. Moshe,Katz-Brull, Rachel
supporting information, p. 7076 - 7078 (2013/09/02)
Real-time monitoring of betaine aldehyde metabolism at high temporal resolution was accomplished using a hyperpolarized choline analog and 13C-NMR. This represents the first observation of an aldehyde intermediate on hyperpolarized MR and opens the way for kinetic studies of oxidase/dehydrogenase enzymes in vitro and in vivo.
