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From the laboratory to the field: cholinesterase phosphylation and its subsequent reactivation by oximes in correlation with temperature (CROSBI ID 596473)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Katalinić, Maja ; Šinko, Goran ; Kovarik, Zrinka ; Stojan, Jure From the laboratory to the field: cholinesterase phosphylation and its subsequent reactivation by oximes in correlation with temperature // 14th Medical Chemical Defence Conference 2013: Translation of experimental research for improved treatment of chemical warfare agent poisoning, Munchen, Njemačka, Programm. 2013. str. 53-x

Podaci o odgovornosti

Katalinić, Maja ; Šinko, Goran ; Kovarik, Zrinka ; Stojan, Jure

engleski

From the laboratory to the field: cholinesterase phosphylation and its subsequent reactivation by oximes in correlation with temperature

The importance of cholinesterases (AChE, EC 3.1.1.7 and BChE, EC 3.1.1.8) in maintaining the homeostasis of an organism has been investigated and presented ever since their discovery. Even now, many new roles for these enzymes are being considered and described. Since many of the in vitro experiments concerning cholinesterases are performed at a lower temperature than the physiological one, a translation of the obtained experimental results to in vivo conditions presents a great challenge. Namely, activity of cholinesterases as enzymes displays a certain temperature optimum, in other words, all kinetic parameters describing cholinesterase activity and their interactions with ligands are temperature dependent. We focused our study on the thermodynamic characterization of cholinesterase interactions with organophosphorus pesticides and nerve agents, and the subsequent reactivation of phosphylated cholinesterases by oximes. The threat of a misuse of these highly toxic organophosphorus compounds (OPs) is still widely present. On the other hand, oximes as antidotes are characterised as orphan drugs, which further raises a wide array of concerns that should be addressed even in the early phases of antidote development. Therefore, a critical view is required for in vitro obtained experimental results in this area of research. The main goal of our study was to define a temperature-correlated model of cholinesterase phosphylation as well as of oxime-assisted reactivation. Such a model could prove valuable for estimating kinetic data at a desired temperature, for example the physiological one, based on the experiments performed at more convenient temperatures. It would also ensure a better selection of compounds for in vivo experiments. Furthermore, knowing the manner in which the properties of cholinesterases alter within a temperature range could improve the development of cholinesterase-based agents for OP decontamination. Acknowledgment This work was supported by the Croatian-Slovenian bilateral project 2012-2013 (PIs: G. Šinko, J. Stojan).

thermodynamic characterization; reactivation; oximes

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Podaci o prilogu

53-x.

2013.

objavljeno

Podaci o matičnoj publikaciji

14th Medical Chemical Defence Conference 2013: Translation of experimental research for improved treatment of chemical warfare agent poisoning, Munchen, Njemačka, Programm

Podaci o skupu

14th Medical Chemical Defence Conference 2013: Translation of experimental research for improved treatment of chemical warfare agent poisoning

poster

23.04.2013-25.04.2013

München, Njemačka

Povezanost rada

Kemija