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

Biomolecules