Phen-DC3 Induces Refolding of Human Telomeric DNA into a Chair-Type Antiparallel G-Quadruplex through Ligand Intercalation

Anirban Ghosh, Central European Institute of Technology at Masaryk University (CEITEC) MU 

Human telomeric G-quadruplex DNA structures are attractive anticancer drug targets. Still, 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 showed 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.

Angew Chem Int Ed Engl. 2022 Oct 4;61(40):e202207384. doi: 10.1002/anie.202207384.

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