Ru-indoloquinoline complex as a selective and effective human telomeric G-quadruplex binder

Spectrochim Acta A Mol Biomol Spectrosc. 2014 Nov 11;132:84-90. doi: 10.1016/j.saa.2014.04.160. Epub 2014 May 9.

Abstract

Indoloquinoline and its derivatives have been reported to be a kind of efficient G-quadruplex binder and have been found to interact preferentially to intramolecular G-quadruplex and inhibit telomerase activity in human K562 cells and SW620 cells. In contrast to indoloquinoline derivatives, much less is known about the metal complex based on indoloquinoline or its derivative. In this report, we studied the interaction of ruthenium complex [Ru(bpy)2(itatp)]2+ containing indoloquinoline moiety with human telomeric G-quadruplex DNA (Telo22) and c-myc G-quadruplex DNA (Pu27) by UV-visible (UV-Vis), fluorescence spectroscopy, fluorescent intercalator displacement (FID), thermal denaturation studies and CD spectroscopy. The results suggest that [Ru(bpy)2(itatp)]2+ displays a strong π-π stacking interaction with human telomeric G-quadruplex with a high binding constant (∼10(7) M(-1)), but just exhibits moderate binding affinity to c-myc G-quadruplex, thus showing significant selectivity to human telomeric G-quadruplex. The CD titration results indicate that [Ru(bpy)2(itatp)]2+ could effectively convert Telo22 into antiparallel G-quadruplex conformation, while in the c-myc G-quadruplex case, instead of promoting Pu27 to fold into G-quadruplex, [Ru(bpy)2(itatp)]2+ destroys the parallel G-quadruplex structure of Pu27.

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
  • Coordination Complexes / metabolism*
  • Flame Ionization
  • G-Quadruplexes*
  • Humans
  • K562 Cells
  • Nucleic Acid Denaturation
  • Quinolines / chemistry*
  • Ruthenium / chemistry
  • Ruthenium / metabolism*
  • Spectrometry, Fluorescence
  • Telomere / metabolism*
  • Time Factors
  • Titrimetry

Substances

  • Coordination Complexes
  • Quinolines
  • Ruthenium