Solution structure of an intramolecular (3 + 1) human telomeric G-quadruplex bound to a telomestatin derivative

J Am Chem Soc. 2013 Sep 11;135(36):13495-501. doi: 10.1021/ja405843r. Epub 2013 Aug 27.


Guanine-rich human telomeric DNA can adopt secondary structures known as G-quadruplexes, which can be targeted by small molecules to achieve anticancer effects. So far, the structural information on complexes between human telomeric DNA and ligands is limited to the parallel G-quadruplex conformation, despite the high structural polymorphism of human telomeric G-quadruplexes. No structure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here we present the first high-resolution structure of the complex between an intramolecular (3 + 1) human telomeric G-quadruplex and a telomestatin derivative, the macrocyclic hexaoxazole L2H2-6M(2)OTD. This compound is observed to interact with the G-quadruplex through π-stacking and electrostatic interactions. This structural information provides a platform for the design of topology-specific G-quadruplex-targeting compounds and is valuable for the development of new potent anticancer drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • G-Quadruplexes*
  • Humans
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Oxazoles / chemistry*
  • Solutions
  • Telomere / chemistry*


  • Oxazoles
  • Solutions
  • telomestatin