A study on a telo21 G-quadruplex DNA specific binding ligand: enhancing the molecular recognition ability via the amino group interactions

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).