The changes in structure and dynamics of oncogenic (c-MYC) and telomeric (h-TELO) G-rich DNA sequences due to the binding of a novel carbazole derivative (BTC) are elucidated using single-molecule Förster resonance energy transfer (sm-FRET), fluorescence correlation spectroscopy (FCS) and NMR spectroscopy. In contrast to the previous reports on the binding of ligands to pre-folded G-quadruplexes, this work illustrates how ligand binding changes the conformational equilibria of both unstructured G-rich DNA sequences and K+-folded G-quadruplexes. The results demonstrate that K+ free c-MYC and h-TELO exist as unfolded and partially folded conformations. The binding of BTC shifts the equilibria of both investigated DNA sequences towards the folded G-quadruplex structure, increases the diffusion coefficients and induces faster end-to-end contact formation. BTC recognizes a minor conformation of the c-MYC quadruplex and the two-tetrad basket conformations of the h-TELO quadruplex.
Debnath, M., Ghosh, S., Panda, D., Bessi, I., Schwalbe, H., Bhattacharyya, K., & Dash, J. (2016). Small molecule regulated dynamic structural changes of human G-quadruplexes. Chemical Science, 7(5), 3279–3285. https://doi.org/10.1039/c6sc00057f