Naslov
Structure-activity approach in the reactivation of tabun-phosphorylated human acetylcholinesterase with bispyridinium para-aldoximes

Autori
Kovarik, Zrinka ; Čalić, Maja ; Šinko, Goran ; Bosak, Anita

Izvornik
Arhiv za higijenu rada i toksikologiju (0004-1254) 58 (2007), 2; 201-209

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
antidotes; nerve agents; organophosphorus compounds

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA