Phen‐DC ₃ Induces Refolding of Human Telomeric DNA into a Chair‐Type Antiparallel G‐Quadruplex through Ligand Intercalation

Human telomeric G-quadruplex DNA structures are attractive anticancer drug targets, but the target's polymorphism complicates design: different ligands prefer folds, and very few complexes have been solved at high resolution. Here we report that Phen-DC3, one of most prominent in terms binding affinity selectivity, causes dTAGGG(TTAGGG)3 to completely change its fold KCl solution from a hybrid-1 an antiparallel chair-type structure, wherein ligand intercalates between two-quartet unit pseudo-quartet, thereby ejecting potassium ion. This unprecedented high-resolution NMR structure shows for first time true intercalation into intramolecular G-quadruplex.