A bridged azobenzene derivative exhibits fully-reversible photocontrolled binding to a G-quadruplex DNA/duplex junction

The ability to control G-quadruplex (G4) conformation using light as an external stimuli offers unique opportunities to control G4 in biological settings and for the development of nucleotide-based nanodevices. We describe a novel G4-binding chemotype derived from a cyclic azobenzene core that reversibly photoisomerises between E- and Z- under physiological conditions. We demonstrate the selective binding of the E-ligand towards LTR-III G4 and show that binding and dissociation from the LTR-III G4 can be controlled reversibly by alternate irradiation with blue and green light. Interestingly, the different isomers exhibit very distinct binding modes. Whilst the (E)-ligand preferentially binds at the G4/duplex junction of the LTR-III sequence, the (Z)-isomer favours the duplex region.