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Recombinant Human Erythropoietin Proteins Synthesized in Escherichia coli Cells: Effects of Additional Domains on the in vitro and in vivo Activitiesстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 21 февраля 2019 г.
- Авторы: Karyagina A.S., Grunina T.M., Lyaschuk A.M., Voronina E.V., Marigin R.A., Cherepushkin S.A., Trusova I.N., Grishin A.V., Poponova M.S., Orlova P.A., Manskikh V.N., Strukova N.V., Generalova M.S., Nikitin K.E., Soboleva L.A., Boksha I.S., Gromov A.V.
- Журнал: Biochemistry (Moscow)
- Том: 84
- Номер: 1
- Год издания: 2019
- Издательство: Pleiades Publishing, Ltd
- Местоположение издательства: Road Town, United Kingdom
- Первая страница: 20
- Последняя страница: 32
- DOI: 10.1134/S0006297919010036
- Аннотация: The aim of this work was to compare biological activities of three variants of bacterially expressed human recombinant erythropoietin (EPO) with additional protein domains: 6His-s-tag-EPO protein carrying the s-tag (15-a.a. oligopeptide from bovine pancreatic ribonuclease A) at the N-terminus and HBD-EPO and EPO-HBD proteins containing heparin-binding protein domains (HBD) of the bone morphogenetic protein 2 from Danio rerio at the N- and C-termini, respectively. The commercial preparation Epostim (LLC Pharmapark, Russia) produced by synthesis in Chinese hamster ovary cells was used for comparison. The EPO variant with the C-terminal HBD domain connected by a rigid linker (EPO-HBD) possesses the best properties as compared to HBD-EPO with the reverse domain arrangement. It was ~13 times more active in vitro (i.e., promoted proliferation of human erythroleukemia TF-1 cells) and demonstrated a higher rate of association with the erythropoietin receptor. EPO-HBD also exhibited the greatest binding to the demineralized bone matrix (DBM) and more prolonged release from the DBM among the four proteins studied. Subcutaneous administration of EPO-HBD immobilized on DBM resulted in significantly more pronounced vascularization of surrounding tissues in comparison with the other proteins and DBM alone. Therefore, EPO-HBD displayed better performance with regard to all the investigated parameters than other examined EPO variants, and it seems promising to study the possibility of its medical use.
- Добавил в систему: Карягина-Жулина Анна Станиславовна