Beatrice Karg, "Rational Design of G-Quadruplex Topologies: How to play with DNA structures"

Monday 21 Oct 2019, 15:00 → 17:00 Europe/Zurich

DNA can adopt a variety of secondary structures. Notably, guanine-rich sequences can
fold into quadruplex structures consisting of G-tetrads instead of base pairs. These
G-quadruplexes (G4) show great diversity in strand orientation and nucleoside confor-
mation depending on sequence and environmental conditions. G-quadruplexes have also
been demonstrated to be of relevance in both gene regulation and oncogenesis.
NMR spectroscopy constitutes a powerful tool to study these structures. Employing a
combination of various NMR techniques we can not only illuminate quadruplex topolo-
gies but also assess ligand binding to the G4 structures. Furthermore, time and temper-
ature dependent measurements allow for studies on G4 dynamics and enthalpy changes
during conformational interconversions.
Here, a comprehensive exploration of quadruplex folding and dynamics is presented for
a G4 that is based on the c-MYC sequence from the promotor region of the NHE III
element. By incorporating 8-Br-guanosine analogs with their strong propensity for a
syn conformation at speci?c positions within the G4 core, transition energies during
folding and relative stabilities of conformers can be manipulated to allow for speci?c
conformational and topological changes.