Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding

Angew Chem Int Ed Engl. 2017 Jun 12;56(25):7102-7106. doi: 10.1002/anie.201702135. Epub 2017 May 19.


Telomeric G-quadruplexes have recently emerged as drug targets in cancer research. Herein, we present the first NMR structure of a telomeric DNA G-quadruplex that adopts the biologically relevant hybrid-2 conformation in a ligand-bound state. We solved the complex with a metalorganic gold(III) ligand that stabilizes G-quadruplexes. Analysis of the free and bound structures reveals structural changes in the capping region of the G-quadruplex. The ligand is sandwiched between one terminal G-tetrad and a flanking nucleotide. This complex structure involves a major structural rearrangement compared to the free G-quadruplex structure as observed for other G-quadruplexes in different conformations, invalidating simple docking approaches to ligand-G-quadruplex structure determination.

Keywords: DNA-ligand complexes; G-quadruplexes; NMR spectroscopy; drug design; structure elucidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA / chemistry*
  • G-Quadruplexes*
  • Gold / chemistry
  • Humans
  • Ligands
  • Macromolecular Substances / chemistry*
  • Nucleic Acid Conformation*
  • Organometallic Compounds / chemistry
  • Proton Magnetic Resonance Spectroscopy / methods*
  • Telomere


  • Ligands
  • Macromolecular Substances
  • Organometallic Compounds
  • Gold
  • DNA