Light-driven conformational regulation of human telomeric G-quadruplex DNA in physiological conditions

Abstract

Human telomeric G-quadruplexes have raised broad interest not just due to their involvement in the regulation of gene expressions and telomerase activities but also because of their application in nanoarchitectures. Herein, three azobenzene derivatives 1-3 were synthesized with different substituent groups and their photo-isomerization properties were investigated by UV/Vis spectroscopy. Then circular dichroism spectroscopy (CD), fluorescence experiments and native-gel electrophoresis were performed to evaluate their capabilities of conformational photo-regulation both in the absence and presence of metal ions. The results suggested that the compounds synthesized can successfully regulate the conformation of human telomeric G-quadruplex DNA in K(+) conditions to some extent. This work will initiate the possibility for the design and intriguing application of light-induced switching to photoregulate the conformation of G-quadruplex DNA under physiological conditions, providing a possible pathway to control G-quadruplex conformation in biological applications and also expanding the potential use of G-quadruplexes in nanomachines.

Reversible manipulation of the G-quadruplex structures and enzymatic reactions through supramolecular host–guest interactions

“…The characteristic variations of CD spectra can reflect the conformational changes in DNA. As in our previous study (25,26), the addition of either Razo or Razo-s efficiently induced the conformational conversion of h-Telo from a single-stranded form into a parallel G4 structure, but there was no significant difference in the ability of these two molecules to induce G4 structures (Supplementary Figure S4). Then, we examined the influence of increasing amounts of CB7 on the topological states of h-Telo in the presence of G4 inducers.…”

“…Appropriate operator molecules are required to achieve our goal. On the basis of our previous studies (25,26), Razo and Razo-s show excellent abilities to induce the formation of G4 structures and are therefore selected as the candidates. Molecular modeling studies indicate that the quaternary ammonium groups of Razo are deeply involved in the observed G4 binding (25).…”

“…Razo and Razo-s were synthesized as previously reported (25,26). To prove the feasibility of our concept, h-Telo was tested as a model.…”

“…Recently, photo-induced conformational changes of nucleic acids have been achieved (24). We also reported the reversible light-control of a G4 structure using some azobenzene derivatives, such as Razo and Razo-s (structures shown in Supplementary Figure S2) (25,26). However, the major drawback of the photo-induced process is the depth limit of the excitation beam in tissues and biological systems.…”

A Photoresponsive Stiff‐Stilbene Ligand Fuels the Reversible Unfolding of G‐Quadruplex DNA

“…A notable exception is an azobenzene derivative developed by Wang and co‐workers that permits photoregulation of G4 folding and dissociation in aqueous media by isomerization of the azobenzene scaffold between the cis and the trans forms . However, the effects are significantly diminished under physiologically relevant ionic conditions where the conformational preference exerted by the high concentration of monovalent cations appears more difficult to overcome with a ligand‐driven approach …”