Pregled bibliografske jedinice broj: 428839
Oxime-assisted reactivation of phosphorylated butyrylcholinesterase
Oxime-assisted reactivation of phosphorylated butyrylcholinesterase // 10th International Meeting on Cholinesterases, Šibenik, Hrvatska, Programme and Abstracts / Kovarik, Zrinka (ur.).
Zagreb: Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2009. str. 46-47 (pozvano predavanje, međunarodna recenzija, sažetak, znanstveni)
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Naslov
Oxime-assisted reactivation of phosphorylated butyrylcholinesterase
Autori
Kovarik, Zrinka ; Katalinić, Maja ; Šinko, Goran
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
10th International Meeting on Cholinesterases, Šibenik, Hrvatska, Programme and Abstracts
/ Kovarik, Zrinka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2009, 46-47
ISBN
978-953-95551-3-7
Skup
10th International Meeting on Cholinesterases
Mjesto i datum
Šibenik, Hrvatska, 20.09.2009. - 25.09.2009
Vrsta sudjelovanja
Pozvano predavanje
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
Reactivators; Oximes; Tabun; Inhibition; Butylcholinesterase
Sažetak
Butyrylcholinesterase is considered an endogenous stoichiometric bioscavenger of organophosphorus compounds (OP), but due to a limited concentration of BChE in the organism, a stoichiometric reduction of OP is not always sufficient. This can be improved by creating a pseudo-catalytic scavenger adding oximes as reactivators of inhibited BChE. In order to improve BChE endogenous bioscavenging function in tabun and paraoxon poisoning, we tested in vitro reactivation of phosphorylated human plasma BChE by eleven bispyridinium oximes varying in the length and type of the linker between rings, and in the position of the oxime group on the ring. Among the tested oximes the most potent reactivators of tabun inhibitedBChE were K117 [1, 1'-(2, 2'-oxybis(ethane-2, 1-diyl))bis(4-hydroxyiminomethyl pyridinium) bromide] and K127 [4-carbamoyl-1-(2-(2-(4-(hydroxyiminomethyl) pyridinium-1-yl)ethoxy)ethyl)pyridinium bromide]. Reactivation by these oximes (1 mM) reached about 50 % after only 20 min, but reactivation stopped at 70 %. Reactivation of paraoxon-inhibited BChE was slow by all of the selected oximes. Using molecular mechanics we performed docking of the oximes to tabun- and paraoxon-inhibited BChE. We will discuss possible structural modifications of bispyridinium oximes to improve reactivation of phosphorylated BChE.
Izvorni jezik
Engleski
Znanstvena područja
Kemija
POVEZANOST RADA
Projekti:
022-0222148-2889 - Interakcije organofosfata, karbamata i određenih liganada s esterazama (Kovarik, Zrinka, MZOS ) ( CroRIS)
Ustanove:
Institut za medicinska istraživanja i medicinu rada, Zagreb
