vestibИзвестия Национальной академии наук Беларуси. Серия биологических наукProceedings of the National Academy of Sciences of Belarus, Biological Series1029-89402524-230XThe Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"vestib-267Research ArticleСтатьиСИНТЕЗ ФЛУДАРАБИН-5′-МОНОФОСФАТА С ИСПОЛЬЗОВАНИЕМ БАКТЕРИАЛЬНЫХ РЕКОМБИНАНТНЫХ ФЕРМЕНТОВSYNTHESIS OF FLUDARABINE 5′-MONOPHOSPHATE USING BACTERIAL RECOMBINANT ENZYMESБересневА. И.BeresnevA. I.

канд. биол. наук, ст. науч. сотрудник

Ph. D. (Biol.), Senior scientific researcher. Institute of Microbiology

andrey_beresnev@mbio.bas-net.byРымкоА. Н.RymkoA. N.

канд. биол. наук, ст. науч. сотрудник

Ph. D. (Biol.), Senior scientific researcher. Institute of Microbiology

ingecate@mail.ruЕрошевскаяЛ. А.EroshevskayaL. A.

канд. биол. наук, вед. науч. сотрудник

Ph. D. (Biol.), Lead scientific researcher. Institute of Microbiology

ljarosha@yandex.comКвачС. В.KvachS. V.

канд. биол. наук, вед. науч. сотрудник

Ph. D. (Biol.), Lead scientific researcher. Institute of Microbiology

Sergkvach@mbio.bas-net.byКвасюкЕ. И.KvasyukE. I.

д-р хим. наук, профессор

D. Sc. (Chem.), Professor

ekvasyuk@inbox.ruЗинченкоА. И.ZinchenkoA. I.

чл.-кор., д-р биол. наук, профессор, заведующий лабораторией

Corresponding Member, D. Sc. (Biol.), Professor, Head of the laboratory

zinch@mbio.bas-net.beИнститут микробиологии НАН БеларусиInstitute of Microbiology of the National Academy of Sciences of BelarusМеждународный государственный экологический институт им. А. Д. Сахарова БГУInternational State Ecological Institute named after A. D. Sakharov of the Belarusian State University20171802201701715Copyright © Береснев А.И., Рымко А.Н., Ерошевская Л.А., Квач С.В., Квасюк Е.И., Зинченко А.И., 20172017Береснев А.И., Рымко А.Н., Ерошевская Л.А., Квач С.В., Квасюк Е.И., Зинченко А.И.Beresnev A.I., Rymko A.N., Eroshevskaya L.A., Kvach S.V., Kvasyuk E.I., Zinchenko A.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestibio.belnauka.by/jour/article/view/267

Разработана и экспериментально обоснована схема ферментативного получения флударабин-5′-монофосфата из 2-фтораденина и циклоцитидина как донора арабинозного фрагмента. При этом донором фосфатной группы служил ацетилфосфат. В качестве биокатализаторов применяли цитидиндезаминазу, уридинфосфорилазу, пуриннуклеозидфосфорилазу и дезоксинуклеозидкиназу, выделенные из клеток ранее сконструированных штаммов Escherichia coli. Полученный препарат флударабин-5′-монофосфата планируется использовать в качестве пролекарства в разрабатываемом ферментативном пролекарственном подходе к терапии рака.

 

The scheme of enzymatic preparation of fludarabine-5′-monophosphate from 2-fluoroadenine and cyclocytidine as a donor of arabinose fragment was developed and experimentally proved. Acetylphosphate was used as a donor of phosphate group. Cytidine deaminase, uridine phosphorylase, purine nucleoside phosphorylase and deoxynucleoside kinase recovered from earlier designed strains of Escherichia coli were used as biocatalysts. The synthesized fludarabine-5′-monophosphate is planned for using as a pro-drug in enzymatic pro-medicinal approach to therapy of cancer.

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The authors declare that there are no conflicts of interest present.