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Discrimination between G/C Binding Sites by Olivomycin A Is Determined by Kinetics of the Drug-DNA Interactionстатья
Статья опубликована в высокорейтинговом журнале
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: 25 ноября 2020 г.
- Авторы: Beniaminov Artemy D., Chashchina Galina V., Livshits Mikhail A., Kechko Olga I., Mitkevich Vladimir A., Mamaeva Olga K., Tevyashova Anna N., Shtil Alexander A., Shchyolkina Anna K., Kaluzhny Dmitry N.
- Журнал: International Journal of Molecular Sciences
- Том: 21
- Номер: 15
- Год издания: 2020
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 5299
- Последняя страница: 5299
- DOI: 10.3390/ijms21155299
- Аннотация: Olivomycin A (OA) exerts its cytotoxic potency due to binding to the minor groove of the G/C-rich DNA and interfering with replication and transcription. Screening of the complete set of tetranucleotide G/C sites by electrophoretic mobility gel shift assay (EMSA) revealed that the sites containing central GC or GG dinucleotides were able to bind OA, whereas the sites with the central CG dinucleotide were not. However, studies of equilibrium OA binding in solution by fluorescence, circular dichroism and isothermal titration calorimetry failed to confirm the sequence preference of OA, indicating instead a similar type of complex and comparable affinity of OA to all G/C binding sites. This discrepancy was resolved by kinetics analysis of the drug–DNA interaction: the dissociation rate significantly differed between SGCS, SGGS and SCGS sites (S stands for G or C), thereby explaining the disintegration of the complexes during EMSA. The functional relevance of the revealed differential kinetics of OA–DNA interaction was demonstrated in an in vitro transcription assay. These findings emphasize the crucial role of kinetics in the mechanism of OA action and provide an important approach to the screening of new drug candidates.
- Добавил в систему: Страховская Марина Глебовна