Neomycin-capped aromatic platforms: quadruplex DNA recognition and telomerase inhibition

Org Biomol Chem. 2006 Mar 21;4(6):1049-57. doi: 10.1039/b516378a. Epub 2006 Jan 25.


A series of aminoglycoside-capped macrocyclic structures has been prepared using intramolecular bis-tethering of neomycin on three aromatic platforms (phenanthroline, acridine, quinacridine). Based on NMR and calculations studies, it was found that the cyclic compounds adopt a highly flexible structure without conformational restriction of the aminoglycoside moiety. FRET-melting stabilization measurements showed that the series displays moderate to high affinity for the G4-conformation of human telomeric repeats, this effect being correlated with the size of the aromatic moiety. In addition, a FRET competition assay evidenced the poor binding ability of all macrocycles for duplex DNA and a clear binding preference for loop-containing intramolecular G4 structures compared to tetramolecular parallel G4 DNA. Finally, TRAP experiments demonstrated that the best G4-binder (quinacridine ) is also a potent and selective telomerase inhibitor with an IC(50) in the submicromolar range (200 nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemistry
  • Carbohydrate Conformation
  • DNA / chemistry*
  • Fluorescence Resonance Energy Transfer
  • Hydrocarbons, Aromatic / chemistry*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Neomycin / chemistry*
  • Neomycin / pharmacology*
  • Phenanthrolines / chemistry
  • Quinacrine / chemistry
  • Taq Polymerase / metabolism
  • Telomerase / antagonists & inhibitors*


  • Acridines
  • Hydrocarbons, Aromatic
  • Phenanthrolines
  • DNA
  • Taq Polymerase
  • Telomerase
  • Quinacrine
  • Neomycin