A bichromophoric squaraine based NIR fluorescent probe for G-quadruplex in living cells

Abstract

The polymorphic formation of G-quadruplex brings more attentions, because changes of formation sites affect many physiological processes, like telomere maintenance, transcription and DNA replication. These processes are highly susceptible to ROS-induced oxidative damage. In this work, bichromophoric cores of symmetric squaraine probe SQ linked with ether chain is conducive to the recognition of G-quadruplex, based on the mechanism of intra or intermolecular “aggregation-disaggregation”. Several interaction behaviors, such as self-aggregation, binding affinity, stoichiometric ratio, were fully investigated via spectrum titration, circular dichroism, fluorescent intercalator displacement assay, and molecular docking. Furthermore, tracking G-quadruplex distribution in the cytoplasm was monitored by SQ during the oxidative stress enhancement. Interestingly, the G-quadruplex levels in the cytoplasm of cancer cells were slightly higher than that of normal cells to deal with oxidation-reduction imbalance. Overall, the lower detection limit of SQ for parallel G-quadruplex like pu27 is as low as 7.2 nM; and the complex of SQ and G-quadruplex will not change the topological structure of G-quadruplex. It has good sensitive and stability for parallel type of G-quadruplex. It is a potential tool for bioimaging of G-quadruplex in the cytoplasm.