Polarity inversion sensitized G-quadruplex metal sensors with K+ tolerance

Due to the high abundance of K + in environments and K + -induced high stability of G-quadruplex (G4), developing a selective G4-based fluorescent sensor for other metal ions with K + tolerance is a great challenge. Herein, we found that even in the presence of 15000-fold excess of K + , Ba 2+ exhibits a highly specific binding with a human telomeric G4 (htG4) in comparison with other G4-binding metal ions such as Pb 2+ and Sr 2+ . This specific binding event can be recognized by a natural fluorophore of hypericin with a lighting-up fluorescence response. Interestingly, inverting the polarity of the most 3' G in htG4 can sensitize the Ba 2+ response with the retaining Ba 2+ specificity and K + tolerance. This polarity inversion of htG4 causes a G4 conformation change in K + and the polarity-inverted htG4 tends to favorably dimerize in response to the Ba 2+ specific binding. To our knowledge, this is the first report that polarity inversion of G4 can be applied to construct a selective metal sensor with K + tolerance. Our findings will open a new way to conveniently regulate the G4 conformation and stability by polarity inversion towards developing high-performance sensors.