A symmetric ligand is synthesized composed of a core N-methylpyridinium scaffold and two para-substituted benzyl groups through a flexible ethylene bridge to form a novel three-ring-conjugated system. The ligand system was found to have only weak background fluorescent signal in aqueous or physiological conditions and exhibited strong fluorescent signal enhancement targeting at telo21 G-quadruplex structure rather than other types of nucleic acids. The comparison study with two terminal groups (-N(CH3)2 versus -SCH3) indicates that the stimulated signal enhancement of specific binding is probably attributed to the hydrogen-bonding interactions through the amino groups in the G-quartets. The docking result illuminates the experimental observation that the ligand system showed only weak fluorescent signals in aqueous or physiological conditions while exhibiting a strong fluorescent signal upon binding to the telo21 G-quadruplex structure (binding energy: -6.2 kcal mol-1).
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