A Light‐up Logic Platform for Selective Recognition of Parallel G‐Quadruplex Structures via Disaggregation‐Induced Emission

Abstract

The design of turn‐on dyes with optical signals sensitive to the formation of supramolecular structures provides fascinating and underexplored opportunities for G‐quadruplex (G4) DNA detection and characterization. Here, we show a new switching mechanism that relies on the recognition‐driven disaggregation (on‐signal) of an ultrabright coumarin‐quinazoline conjugate. The synthesized probe selectively lights‐up parallel G4 DNA structures via the disassembly of its supramolecular state, demonstrating outputs that are easily integrable into a label‐free molecular logic system. Finally, our molecule preferentially stains the G4‐rich nucleoli of cancer cells.

A site-specific self-assembled light-up rotor probe for selective recognition and stabilization of c-MYC G-quadruplex DNA

“…[1][2][3]12 Supramolecular fluorescence sensors with distinguishable and controllable readout responses were recently designed as topology-specific G4-binders. [13][14][15][16] Their G4-interactive binding model relies on the disassembly of the molecular aggregate (disaggregation-induced emission, DIE) in the presence of highly accessible π-surfaces such as those found in parallel G4 topologies. Parallel G4 structures are devoid of either adjacent lateral or diagonal loops, and can therefore provide better π-stacking platforms for the accommodation of the aromatic core of these ligands.…”

Unravelling the cellular emission fingerprint of the benchmark G-quadruplex-interactive compound Phen-DC3

“…4A and B). 16,19,21,22 The observed staining pattern was independent of the fixation method, as Phen-DC 3 -treated cells fixed with MeOH showed a similar staining pattern but with reduced cytoplasmic signal (Fig. S8, ESI †).…”

“…This LOD value, even if slightly higher compared to the most sensitive light-up G4 probes reported so far, still falls within the nanomolar range and provides possibilities to probe G4 formation in a cellular context. 16,19,20 The treatment of PFA-fixed HeLa cells with Phen-DC 3 showed an intense fluorescence signal in the cytoplasmic and nuclear regions with clear peaks in the subnuclear compartments whose appearance is compatible with nucleoli ( Fig. 4A and B).…”

“…The phenanthroline dicarboxamide bisquinolinium compound, Phen-DC 3 , is one of the most potent G4-binders reported so far and is used as a benchmark compound in a wide number of studies to probe G4 formation in vitro and in cellular systems. [6][7][8][9][10][11][12][13][14][15][16] Its overall crescent-like bent shape ensures an extensive overlap with the guanines on the terminal G-quartets and prevents intercalation between the Watson-Crick base pairs in duplex DNA, therefore limiting off-target binding interactions ( Fig. 1).…”

Preparation and photophysical properties of quinazoline-based fluorophores

“…Taking advantage of this disaggregation-induced emission (DIE), a turn-on uorescent probe was designed and was capable of probing parallel G4 DNA topologies over other G4 DNA structures. 16 However, in contrast to frequently used electron-decient benzothiadiazole (BTD), 17 the uorescent compounds based on quinazolines largely remained immature. The same goes for the uorescent structure-property relationship (FSPR) 18,19 studies which are instructive in the development of new uorophores with a unique application.…”