Interactions of ruthenium complexes containing indoloquinoline moiety with human telomeric G-quadruplex DNA

Spectrochim Acta A Mol Biomol Spectrosc. 2014 Apr 24;124:187-93. doi: 10.1016/j.saa.2013.12.096. Epub 2014 Jan 7.

Abstract

G-quadruplex structures are attractive targets for the development of anticancer drugs, as their formation in human telomere could impair telomerase activity, thus inducing apoptosis in cancer cells. Vast majority of G-quadruplex binding molecules have been designed and synthesized. Ruthenium complexes have also been reported to induction or stabilization of G-quadruplex structure of human telomeric sequence, whereas most of them generally promote the formation of antiparallel or hybrid-type G-quadruplex structure. Ruthenium complex that selectively promotes the formation of parallel G-quadruplex structure has rarely been reported. We reported here the interaction of two ruthenium complexes [Ru(bpy)2(mitatp)](2+)1 and [Ru(phen)2(mitatp)](2+)2 (bpy=2,2' bipyridine, phen=1,10-phenanthroline, mitatp=5-methoxy-isatino[1,2-b]-1,4,8,9-tetraazatriphenylene) containing indoloquinoline moiety with human telomeric G-quadruplex DNA (Telo22). Complex 1 binds to Telo22 tightly via a stable π-π stacking interaction and efficiently stabilizes the G-quadruplex structure. Circular dichroism (CD) spectra titration results suggest that complex 1 could induce Telo22 to fold into antiparallel G-quadruplex conformation. Complex 2 exhibits moderate G-quadruplex binding and stabilizing ability, while CD titration data reveals that complex 2 could promote the formation of parallel G-quadruplex structure.

Keywords: G-quadruplex; Indoloquinoline; Ruthenium complex; Telomere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption, Physicochemical
  • Circular Dichroism
  • Coordination Complexes / chemistry*
  • Flame Ionization
  • Fluorescence Resonance Energy Transfer
  • G-Quadruplexes*
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Humans
  • Luminescence
  • Phenanthrolines / chemistry*
  • Quinolines / chemistry*
  • Ruthenium / chemistry*
  • Telomere / metabolism*
  • Titrimetry
  • Transition Temperature

Substances

  • Coordination Complexes
  • Heterocyclic Compounds, 4 or More Rings
  • Phenanthrolines
  • Quinolines
  • Ruthenium