BENZO[C]PHENANTHRIDINE ALKALOIDS AND THEIR INTERACTION TO NON-CANONICAL DNA STRUCTURES


Petra JAROŠOVÁ^1, Raimundo GARGALLO^2, Petr TÁBORSKÝ^1, Ondřej PEŠ^3


^1Department of Chemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech
Republic

^2Department of Chemical Engineering and Analytical Chemistry, University of Barcelona, Martí I
Franquès 1-11, 08028 Barcelona, Spain

^3Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno,
Czech Republic

Email of presenting author: 408846@mail.muni.cz


Non-canonical DNA secondary structures have become possible therapeutic targets in recent years.
The most known types of these structures are the G-quadruplex (GQ) which is present in several
protooncogenic-DNA promoters and thus participates in biological processes such as replication,
transcription and translation and i-motif, which is sequence observed in cytosin‑rich parts of the
strand and is stable in lower pH conditions. The interaction of natural benzo[c]phenanthridine
alkaloids (macarpine and sanguinarine) with parallel and antiparallel G‑quadruplex DNA structures
was studied, for comparison the competitive dialysis experiment with alkaloid berberine in lower pH
was performed. Spectroscopically-monitored melting experiments, fluorescence titrations and
competitive dialysis were used to observe the interaction of the oligonucleotides and alkaloids.
The results showed that these alkaloids stabilized G-quadruplex structures in terms of increments
of T[m] values with high selectivity over duplexes and unfolded DNA. The presence of non-specific
electrostatic interactions was also observed. Overall, the results pointed to a strong
stabilization of G-quadruplex structures by these alkaloids.



Acknowledgements

This work was supported by department of chemistry, Masaryk University. Part of the work was
carried out with 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.