Naslov
Mutagenesis of acetylcholinesterase enables oxime- assisted reactivation of soman-enzyme conjugate that resist aging

Autori
Maček, Nikolina ; Radić, Zoran ; Taylor, Palmer ; Kuča, Kamil ; Kovarik, Zrinka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the FEBS3+ Meeting ˝From molecules to life and back˝, Opatija, Hrvatska / Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka - Rijeka : Hrvatsko Društvo za Biotehnologiju, 2012

ISBN
978-953-95551-4-4

Skup
FEBS3+ Meeting: From molecules to life and back

Mjesto i datum
Opatija, Hrvatska, 13.06.2012. - 16.06.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
therapeutic treatment; soman; mutants; reactivation

Sažetak
In the event of poisoning by organophosphorus compounds (OP), immediate therapeutic treatment usually consists of combined administration of an anticholinergic drug, such as atropine, and an oxime-reactivator of acetylcholinesterase (AChE, E.C. 3.1.1.7). However, the treatment is very limiting in case of nerve agent soman poisoning due to extremely rapid aging of phosphorylated enzyme. For now, HI-6 is the best known reactivator of soman inhibited AChE. Today, because of limited reactivation of phosphorylated AChE and fast ageing, researches are pointed towards AChE bioscavangers, human AChE mutants among other enzymes. The mutant of our interest is Y337A/F338A where increased accessibility of the Y337A mutation to oximes is combined with aging resisting the F338A mutation. We screened 35 oximes (1mM) for the reactivation activity of soman inhibited human AChE mutant, Y337A/F338A. Only 15 oximes were able to restore more than 30% of soman inhibited Y337A/F338A activity. None of the tested oximes restored Y337A/F338A activity fully nor any of those oximes were better than HI- 6 despite the fact that some of these oximes have CH2-O-CH2 linking chain and/or oxime group in position 2, which is known to be characteristic for the most potent reactivators of soman inhibited AChE. In fact, some of the most potent reactivators among tested oximes have benzene ring in the linking chain so our findings could point the quest for reactivators of soman inhibited AChE and AChE mutants in new direction.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA