Synergically Remodeling Human Telomeric G-Quadruplexes into DNA Mimics of GFP with a Na⁺ Selectivity

DNA/RNA mimics of fluorescent proteins (DMFPs and RMFPs) have been exogenously screened for inspiring variant applications by specifically binding to chromophore analogues to activate their fluorescence. Considerable DMFPs and RMFPs form G-quadruplex (G4) or G4-like structures to accommodate FP chromophore analogues. Therefore, efforts ought to be made to investigate whether these FP chromophore analogues have distinctive interactions with endogenous G4 structures found in natural sequences, such as human telomeric G4s (htG4s). Herein, we found that htG4s can specifically interact with one of the hydroxyethylamino-benzylidene cyanophenyl chromophore derivatives (HBC514) to serve as DNA mimics of green FPs (DMGFPs). Importantly, Na⁺ is required to remodel the K⁺-favored hybrid htG4s into antiparallel htG4s-based DMGFPs with the synergic binding of HBC514. Furthermore, HBC514 most likely aggregates on DMGFPs into an AIEgen with suppressed intramolecular rotation to cause a 2 orders of magnitude enhancement in its fluorescence. Based on the Na⁺-specific DMGFPs, a selective Na⁺ sensor was developed with the potential to tolerate high K⁺ abundance using HBCs as the bifunctional G4-inducer and fluorescent reporter. The DMGFPs conquer the long-standing challenge of developing practical Na⁺ sensors that can be used in physiological environments (for example, serums) with a K⁺-instigated high G4 stability.