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Structure-Activity Approach in the Reactivation of Tabun-Phosphorylated Human Acetylcholinesterase with Bispyridinium para-Aldoximes
Puni tekst: engleski, pdf (253 KB)
Kovarik, Z., Čalić, M., Šinko, G., Bosak, A. (2007). Structure-Activity Approach in the Reactivation of Tabun-Phosphorylated Human Acetylcholinesterase with Bispyridinium para-Aldoximes. Arhiv za higijenu rada i toksikologiju, 58(2). doi:10.2478/v10004-007-0013-7
We investigated interactions of bispyridinium para-aldoximes N,N’-(propano)bis(4-hydroxyiminomethyl) pyridinium bromide (TMB-4), N,N’-(ethano)bis(4-hydroxyiminomethyl)pyridinium methanosulphonate (DMB-4), and N,N’-(methano)bis(4-hydroxyiminomethyl)pyridinium chloride (MMB-4) with human erythrocyte acetylcholinesterase phosphorylated by tabun. We analysed aldoxime conformations to determine the flexibility of aldoxime as an important feature for binding to the acetylcholinesterase active site. Tabun-inhibited human erythrocyte acetylcholinesterase was completely reactivated only by the most flexible bispyridinium aldoxime - TMB-4 with a propylene chain between two rings. Shorter linkers than propylene (methylene or ethylene) as in MMB-4 and DMB-4 did not allow appropriate orientation in the active site, and MMB-4 and DMB-4 were not efficient reactivators of tabun-phosphorylated acetylcholinesterase. Since aldoximes are also reversible inhibitors of native acetylcholinesterase, we determined dissociation constants and their protective index against acetylcholinesterase inactivation by tabun.
antidotes; nerve agents; organophosphorus compounds
Hrčak ID: 12902
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