Structure of a G-quadruplex-ligand complex

J Mol Biol. 2003 Feb 7;326(1):117-25. doi: 10.1016/s0022-2836(02)01354-2.


Stabilisation of G-quadruplex structures formed from telomeric DNA, by means of quadruplex-selective ligands, is a means of inhibiting the telomerase enzyme from catalysing the synthesis of telomeric DNA repeats. In order to understand the molecular basis of ligand-quadruplex recognition, the crystal structure has been determined of such a complex, at 1.75A resolution. This complex is between a dimeric antiparallel G-quadruplex formed from the Oxytricha nova telomeric DNA sequence d(GGGGTTTTGGGG), and a di-substituted aminoalkylamido acridine compound. The structure shows that the acridine moiety is bound at one end of the stack of G-quartets, within one of the thymine loops. It is held in place by a combination of stacking interactions and specific hydrogen bonds with thymine bases. The stability of the ligand in this binding site has been confirmed by a 2ns molecular dynamics simulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemistry*
  • Acridines / metabolism*
  • Animals
  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism*
  • G-Quadruplexes
  • Hydrogen Bonding
  • Ligands
  • Models, Molecular
  • Nucleic Acid Conformation*
  • Oxytricha / genetics
  • Pyrrolidines / chemistry*
  • Pyrrolidines / metabolism*
  • Telomere / chemistry*
  • Telomere / genetics
  • Telomere / metabolism*


  • 3,6-bis-(3-pyrrolidinopropionamide)acridine
  • Acridines
  • Ligands
  • Pyrrolidines
  • DNA