Interaction of metallacrown complexes with G-quadruplex DNA.

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 ~2-5×10(5)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.