7Z9L

Phen-DC3 intercalation causes hybrid-to-antiparallel transformation of human telomeric DNA G-quadruplex

Summary for 7Z9L

• Entry DOI: 10.2210/pdb7z9l/pdb
• NMR Information: BMRB: 34714
• Descriptor: DNA (5'-D(*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*G)-3'), N2,N9-bis(1-methylquinolin-3-yl)-1,10-phenanthroline-2,9-dicarboxamide (2 entities in total)
• Functional Keywords: g quadruplex, ligand intercalation, nmr spectroscopy, mass spectrometry, dna
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 7838.30

Authors

Ghosh, A.,Trajkovski, M.,Teulade-Fichou, M.P.,Gabelica, V.,Plavec, J. (deposition date: 2022-03-21, release date: 2022-08-31, Last modification date: 2024-05-15)

Primary citation

Ghosh, A.,Trajkovski, M.,Teulade-Fichou, M.P.,Gabelica, V.,Plavec, J.
Phen-DC 3 Induces Refolding of Human Telomeric DNA into a Chair-Type Antiparallel G-Quadruplex through Ligand Intercalation.
Angew.Chem.Int.Ed.Engl., 61:e202207384-e202207384, 2022

PubMed 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.

PubMed: 35993443
DOI: 10.1002/anie.202207384

Experimental method

SOLUTION NMR