Synergically\nRemodeling Human Telomeric G‑Quadruplexes\ninto DNA Mimics of GFP with a Na<sup>+</sup> Selectivity

DNA/RNA\nmimics of fluorescent proteins (DMFPs and RMFPs)\nhave been\nexogenously screened for inspiring variant applications by specifically\nbinding to chromophore analogues to activate their fluorescence. Considerable\nDMFPs and RMFPs form G-quadruplex (G4) or G4-like structures to accommodate\nFP chromophore analogues. Therefore, efforts ought to be made to investigate\nwhether these FP chromophore analogues have distinctive interactions\nwith endogenous G4 structures found in natural sequences, such as\nhuman telomeric G4s (htG4s). Herein, we found that htG4s can specifically\ninteract with one of the hydroxyethylamino-benzylidene cyanophenyl\nchromophore derivatives (HBC514) to serve as DNA mimics of green FPs\n(DMGFPs). Importantly, Na<sup>+</sup> is required to remodel the K<sup>+</sup>-favored hybrid htG4s into antiparallel htG4s-based DMGFPs\nwith the synergic binding of HBC514. Furthermore, HBC514 most likely\naggregates on DMGFPs into an AIEgen with suppressed intramolecular\nrotation to cause a 2 orders of magnitude enhancement in its fluorescence.\nBased on the Na<sup>+</sup>-specific DMGFPs, a selective Na<sup>+</sup> sensor was developed with the potential to tolerate high K<sup>+</sup> abundance using HBCs as the bifunctional G4-inducer and fluorescent\nreporter. The DMGFPs conquer the long-standing challenge of developing\npractical Na<sup>+</sup> sensors that can be used in physiological\nenvironments (for example, serums) with a K<sup>+</sup>-instigated\nhigh G4 stability.