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

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2022 Aug 22

PMID 35993443

Authors

Anirban Ghosh

Marko Trajkovski

Marie-Paule Teulade-Fichou

Valerie Gabelica

Janez Plavec

Affiliations

Soon will be listed here.

Abstract

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-DC , one of the most prominent G-quadruplex ligands in terms of high binding affinity and selectivity, causes dTAGGG(TTAGGG) 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.

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