Phen-DC3 Induces Refolding of Human Telomeric DNA into a Chair-Type Antiparallel G-Quadruplex through Ligand Intercalation.
Angew Chem Int Ed Engl
; 61(40): e202207384, 2022 10 04.
Article
em En
| MEDLINE
| ID: mdl-35993443
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-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.Palavras-chave
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1
Base de dados:
MEDLINE
Assunto principal:
Quadruplex G
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article