Quaternary protoberberine alkaloids and their interactions with DNA

Abstract

The G-quadruplex DNA is commonly present in several protooncogenic-DNA promoters and participates in many important biological processes such as replication, transcription, and translation. Because of their supposed role in cancer, G-quadruplex DNA is often studied as a target for anti-cancer drugs. Quaternary protoberberine and tetrahydroprotoberberine alkaloids (corysamine, coptisine, stylopine), which are supposed to selectively bind these structures, have been compared in terms of stability with selected types of DNA. Influence of selected alkaloids on the stability of double-stranded DNA and non-canonical forms of DNA was observed by determining association constants of alkaloid–DNA complexes using spectroscopic methods—molecular absorption spectrometry, fluorescence spectrometry, and mass spectrometry. Furthermore, the effect of given alkaloids on the melting temperature of these DNA structures was determined using CD spectrometry. Competitive dialysis and electrospray mass spectrometry were performed for affinity comparison of certain alkaloids to different DNA structures including G-quadruplexes. These experiments have proven that corysamine and coptisine prefer interaction with G-quadruplexes in comparison to dsDNA and ssDNA, whereas tetrahydroprotoberberine alkaloid stylopine does not interact with any DNA whatsoever.

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Acknowledgements

This work was supported by funds from the Faculty of Medicine MU to a junior researcher Ondřej Peš and by the Specific University Research Grant (MUNI/A/1286/2017, MUNI/A/0976/2018) provided by the Ministry of Education, Youth and Sports of the Czech Republic. The support of Biomolecular Interactions and Crystallization Core facility of CEITEC—Central European Institute of Technology (ID number CZ.1.05/1.1.00/02.0068, financed from European Regional Development Fund) is greatly acknowledged.

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Correspondence to Petr Táborský.

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Jarošová, P., Sándor, R., Slaninková, A. et al. Quaternary protoberberine alkaloids and their interactions with DNA. Chem. Pap. 73, 2965–2973 (2019). https://doi.org/10.1007/s11696-019-00857-z

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Keywords

  • Protoberberine alkaloids
  • Non-canonical structures
  • G-quadruplex
  • dsDNA
  • Competitive dialysis
  • CD
  • Melting temperatures
  • Mass spectrometry