Parallel G-Quadruplex DNA Structures from Nuclear and Mitochondrial Genomes Trigger Emission Enhancement in a Nonfluorescent Nano-aggregated Fluorine–Boron-Based Dye

Abstract

Molecular self-assembly is a powerful tool for the development of functional nanostructures with adaptive optical properties. However, in aqueous solution, the hydrophobic effects in the monomeric units often afford supramolecular architectures with typical side-by-side π-stacking arrangement with compromised emissive properties. Here, we report on the role of parallel DNA guanine quadruplexes (G4s) as supramolecular disaggregating−capture systems capable of coordinating a zwitterionic fluorine−boron-based dye and promoting activation of its fluorescence signal. The dye's high binding affinity for parallel G4s compared to nonparallel topologies leads to a selective disassembly of the dye's supramolecular state upon contact with parallel G4s. This results in a strong and selective disaggregation-induced emission that signals the presence of parallel G4s observable by the naked eye and inside cells. The molecular recognition strategy reported here will be useful for a multitude of affinity-based applications with potential in sensing and imaging systems.

A Cytoplasm‐Specific Fluorescent Ligand for Selective Imaging of RNA G‐Quadruplexes in Live Cancer Cells

“…To investigate whether the identity of mRNA substrates interacted with BYBX in live HeLa cells was G4-structure, we performed a number of intracellular competition assays with the well-known G4-selective ligands including BRACO19 [21,33] and PDS [34] in live HeLa cells. We also conducted colocalization study using BYBX and a G4-specific antibody (BG4) in fixed…”

“…Fluorescent ligands 4 b [18] and 9CI [19] are capable of recognizing c‐MYC DNA G4 ‐ structures selectively. In addition, MitoISCH [20] and 4 b [21] were found to specifically recognize the mitochondrial G‐quadruplex DNA. Nonetheless, with respect to literature, only few RNA G4‐selective fluorescent ligands, such as QUMA‐1 , [22] N‐TASQ , [23] CyT , [24] V‐P1 , [25] and BEDO‐3 , [26] have been reported thus far.…”