Interaction of metallacrown complexes with G-quadruplex DNA

J Inorg Biochem. 2016 Feb:155:105-14. doi: 10.1016/j.jinorgbio.2015.11.025. Epub 2015 Dec 2.

Abstract

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.

Keywords: FID assay; G-quadruplex destabilization; Ligand binding; Metallacrown; Tb(III) luminescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Crown Compounds / chemistry*
  • DNA / chemistry*
  • G-Quadruplexes*
  • Humans
  • Lanthanoid Series Elements / chemistry*
  • Spectrometry, Fluorescence
  • Spectrophotometry, Ultraviolet

Substances

  • Crown Compounds
  • Lanthanoid Series Elements
  • DNA