Cation-Mediated Energy Transfer in G-Quadruplexes Revealed by an Internal Fluorescent Probe

A single pyridine unit incorporated into G-quadruplex DNA has revealed efficient energy transfer reactions in cation-containing G-quadruplexes. 8-(2-Pyridyl)-2'-deoxyguanosine, "2PyG", is a highly sensitive internal fluorescent probe of G-quadruplex folding and energy transfer. 2PyG was minimally disruptive to G-quadruplex folding and exhibited intense fluorescence, even when it was base-stacked with other guanine residues. Using 2PyG we have quantified energy transfer efficiencies within G-quadruplex structures prepared under conditions of excess Na+/K+ (110 mM) or in 40% polyethylene glycol (PEG) under salt deficient conditions. G-quadruplex structures containing coordinated cations exhibited efficient DNA-to-probe energy transfer reactions (eta(t) = 0.11-0.41), while PEG-folded G-quadruplexes exhibited very little energy transfer (eta(t) = 0.02-0.07). Experiments conducted using unmodified G-quadruplexes suggest that cation coordination at the O-6 position of guanine residues results in enhanced quantum yields of G-quadruplex nucleobases that, in turn, serve as efficient energy donors to 2PyG. Given the growing interest in G-quadruplex-based devices and materials, these results will provide important design principles toward harnessing the potentially useful photophysical properties of G-quadruplex wires and other G-rich structures.