Photoregulation of G-quadruplex DNA by non-covalent azobenzene photoswitches

G-quadruplexes (G4) are non-canonical DNA structures involved in important cellular regulatory functions in various genomes, correlated with their folding mechanism. Therefore, the design of small ligands capable of modulating G4 formation/stabilization is of growing interest for the development of new anticancer therapies. In this context, the reversible control of G4s using bistable photoswitches offers promising prospects for applications in photopharmacology but remains largely unexploited. The present project aims to characterize the dynamics of structural changes in G4s triggered by a functionalized azobenzene photoswitch (AZO1), using time-resolved solution X-ray scattering (TR-XSS), an ideal probe to capture changes in DNA 3D conformation. While the properties of AZO1/G4 complexes have been characterized at equilibrium, TR-XSS studies will provide crucial information on non-equilibrium DNA structural changes that will serve as a benchmark for optimization of G4 photoswitches.