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Chemical polysialylation and in vivo tetramerization improve pharmacokinetic characteristics of recombinant human butyrylcholinesterase-based bioscavengers

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dc.contributor.author Terekhov S.
dc.contributor.author Smirnov I.
dc.contributor.author Shamborant O.
dc.contributor.author Bobik T.
dc.contributor.author Ilyushin D.
dc.contributor.author Murashev A.
dc.contributor.author Dyachenko I.
dc.contributor.author Palikov V.
dc.contributor.author Knorre V.
dc.contributor.author Belogurov A.
dc.contributor.author Ponomarenko N.
dc.contributor.author Kuzina E.
dc.contributor.author Genkin D.
dc.contributor.author Masson P.
dc.contributor.author Gabibov A.
dc.date.accessioned 2018-09-18T20:48:14Z
dc.date.available 2018-09-18T20:48:14Z
dc.date.issued 2015
dc.identifier.issn 2075-8251
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/142330
dc.description.abstract © 2015 Park-media, Ltd. Organophosphate toxins (OPs) are the most toxic low-molecular compounds. The extremely potent toxicity of OPs is determined by their specificity toward the nerve system. Human butyrylcholinesterase (hBChE) is a natural bioscavenger against a broad spectrum of OPs, which makes it a promising candidate for the development of DNA-encoded bioscavengers. The high values of the protective index observed for recombinant hBChE (rhBChE) make it appropriate for therapy against OP poisoning, especially in the case of highly toxic warfare nerve agents. Nevertheless, large-scale application of biopharmaceuticals based on hBChE is restricted due to its high cost and extremely rapid elimination from the bloodstream. In the present study, we examine two approaches for long-acting rhBChE production: I) chemical polysialylation and II) in-vivo tetramerization. We demonstrate that both approaches significantly improve the pharmacokinetic characteristics of rhBChE (more than 5 and 10 times, respectively), which makes it possible to use rhBChE conjugated with polysialic acids (rhBChE-CAO) and tetrameric rhBChE (4rhBChE) in the treatment of OP poisonings.
dc.relation.ispartofseries Acta Naturae
dc.subject Biodistribution
dc.subject Biopharmaceutical
dc.subject Bioscavenger
dc.subject Butyrylcholinesterase
dc.subject In vivo tetramerization
dc.subject Pharmacokinetics
dc.subject Polysialylation
dc.title Chemical polysialylation and in vivo tetramerization improve pharmacokinetic characteristics of recombinant human butyrylcholinesterase-based bioscavengers
dc.type Article
dc.relation.ispartofseries-issue 4
dc.relation.ispartofseries-volume 7
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 136
dc.source.id SCOPUS20758251-2015-7-4-SID84951935285


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  • Публикации сотрудников КФУ Scopus [24551]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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