Interaction process behind the strong stabilization of G-quadruplexes by alkaloid fagaronine

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Authors

HANNIG Pavel GARGALLO Raimundo MAZZINI Stefania BORGONOVO Gigliola ZUCCOLO Marco TÁBORSKÁ Eva TÁBORSKÝ Petr

Year of publication 2025
Type Article in Periodical
Magazine / Source Biophysical Chemistry
MU Faculty or unit

Faculty of Science

Citation
web https://www.sciencedirect.com/science/article/pii/S0301462225000559?via%3Dihub
Doi http://dx.doi.org/10.1016/j.bpc.2025.107443
Keywords Fagaronine; G-quadruplex; Fluorescence spectroscopy; Circular dichroism spectroscopy; NMR spectroscopy; Docking simulation
Description Benzo[c]phenanthridine alkaloids are known for their stabilizing effects on non-canonical DNA structures, particularly G-quadruplexes (G4s). In this study, the interaction of fagaronine, a rare benzo[c]phenanthridine alkaloid, with several DNA structures (including B-DNA, parallel, antiparallel and hybrid G4s) is studied using molecular fluorescence and circular dichroism (CD) spectroscopy. It has been found that fagaronine significantly enhances the stability of all tested G4 conformations. Furthermore, a study by NMR spectroscopy provided valuable information on the mechanism of interaction of the ligand with the parallel G4 structure adopted by Pu22T14T23, a sequence mutated with respect to that found within the promoter region of the c-myc gene. Remarkably, when compared with data reported in the literature, fagaronine appears to exhibit one of the strongest G4 thermal stabilization effects ever recorded for a small ligand.
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