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Arhiv za higijenu rada i toksikologiju, Vol. 58 No. 3, 2007.

Pregledni rad
https://doi.org/10.2478/v10004-007-0027-1

Application of Recombinant DNA Methods for Production of Cholinesterases as Organophosphate Antidotes and Detectors

Palmer Taylor
Elsa Reiner
Zrinka Kovarik
Zoran Radić

Puni tekst: engleski, pdf (150 KB) str. 339-345 preuzimanja: 691* citiraj
APA 6th Edition
Taylor, P., Reiner, E., Kovarik, Z. i Radić, Z. (2007). Application of Recombinant DNA Methods for Production of Cholinesterases as Organophosphate Antidotes and Detectors. Arhiv za higijenu rada i toksikologiju, 58 (3), 339-345. https://doi.org/10.2478/v10004-007-0027-1
MLA 8th Edition
Taylor, Palmer, et al. "Application of Recombinant DNA Methods for Production of Cholinesterases as Organophosphate Antidotes and Detectors." Arhiv za higijenu rada i toksikologiju, vol. 58, br. 3, 2007, str. 339-345. https://doi.org/10.2478/v10004-007-0027-1. Citirano 25.05.2019.
Chicago 17th Edition
Taylor, Palmer, Elsa Reiner, Zrinka Kovarik i Zoran Radić. "Application of Recombinant DNA Methods for Production of Cholinesterases as Organophosphate Antidotes and Detectors." Arhiv za higijenu rada i toksikologiju 58, br. 3 (2007): 339-345. https://doi.org/10.2478/v10004-007-0027-1
Harvard
Taylor, P., et al. (2007). 'Application of Recombinant DNA Methods for Production of Cholinesterases as Organophosphate Antidotes and Detectors', Arhiv za higijenu rada i toksikologiju, 58(3), str. 339-345. doi: https://doi.org/10.2478/v10004-007-0027-1
Vancouver
Taylor P, Reiner E, Kovarik Z, Radić Z. Application of Recombinant DNA Methods for Production of Cholinesterases as Organophosphate Antidotes and Detectors. Arh Hig Rada Toksikol. [Internet]. 2007 [pristupljeno 25.05.2019.];58(3):339-345. doi: https://doi.org/10.2478/v10004-007-0027-1
IEEE
P. Taylor, E. Reiner, Z. Kovarik i Z. Radić, "Application of Recombinant DNA Methods for Production of Cholinesterases as Organophosphate Antidotes and Detectors", Arhiv za higijenu rada i toksikologiju, vol.58, br. 3, str. 339-345, 2007. [Online]. doi: https://doi.org/10.2478/v10004-007-0027-1

Sažetak
To develop new avenues for synthesizing novel antidotes for organophosphate poisoning and for detection of the organophosphates, we have turned to recombinant DNA methods to synthesize cholinesterases with unusual properties. For antidotal therapy we describe mutations of the native mouse and human enzymes that allow for enhanced rates of oxime reactivation. Such enzymes, when localized in the circulation, would enable the circulating cholinesterase to become a catalytic rather than simply a stoichiometric scavenger. Hence, “oxime-assisted catalysis” provides a means for scavenging the organophosphates in the circulation thereby minimizing their tissue penetration and toxicity. Accordingly, the oxime antidote or prophylactic agent has a dual action within the circulation and at the tissue level. Second, through a novel chemistry, termed freeze-frame, click chemistry, we have used organophosphate conjugates of acetylcholinesterase as templates for the synthesis of novel nucleophilic reactivating agents. Finally, acetylcholinesterase can be modified through cysteine substitution mutagenesis and attachment of fluorophores at the substitution positions. When linked at certain locations in the molecule, the attached fluorophore is sensitive to organophosphate conjugation with acetylcholinesterase, and thus the very target of insecticide or nerve agent action becomes a detection molecule for organophosphate exposure.

Ključne riječi
acetylcholinesterase; fluorescent acetylcholinesterase; organophosphate inhibitors; oxime antidotes; oxime-assisted catalysis; reactivation kinetics; remote detection; in situ - click chemistry; template-guided drug design

Hrčak ID: 16533

URI
https://hrcak.srce.hr/16533

[hrvatski]

Posjeta: 1.330 *