Interaction of metallacrown complexes with G-quadruplex DNA

• Interactions of G-quadruplex DNA (GQ) with two 15-MC-5 metallacrowns are studied.
• The binding affinities of MCs with G-quadruplex are evaluated (KMC ~ 2–5 × 105 M− 1).
• Binding of MC complexes to GQ DNA causes destabilization of the quadruplex structure.
• A new Tb(III)–GQ quenching assay is proposed to study binding of DNA ligands.

Interactions of the G-quadruplex (GQ) DNA with two pentacoordinate lanthanide (III) metallacrown (MC) complexes containing phenylalanine hydroxamic acid (pheHA) and copper(II) ions of the formula Eu 15-[MCCu,pheHA]-5 (1) and Tb 15-[MCCu,pheHA]-5 (2) were investigated. Binding of both metallacrowns to human telomeric G-quadruplex DNA was followed using CD spectroscopy, DNA melting profiles, and fluorescent intercalator displacement (FID) assay. A new G-quadruplex binding assay based of quenching of Tb(III)–GQ luminescence was proposed and evaluated. All performed tests confirmed interactions of MCs with studied GQ structure. Binding affinities of MCs were appreciable (KMC ~ 2–5 × 105 M− 1). Higher concentration of MCs (the ratio of GQ:MC above 2.5) caused destabilization of tetraplex structure of GQ as evidenced by CD spectroscopy, melting temperatures, and Tb(III)–GQ luminescence quenching results.

Metallacrowns Ln15-MC-5 destabilize G-quadruplex structure of human telomeric DNA.Figure optionsDownload as PowerPoint slide