Affinity and selectivity of G4 ligands measured by FRET.
The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to directly inhibit telomerase activity. The reactivation of this enzyme in immortalized and most cancer cells suggests that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. In this paper, we have analyzed the stabilization and selectivity of two well-known quadruplex ligands (telomestatin and a cationic porphyrin) towards the human telomeric G-quadruplex species, with FRET. Both molecules strongly stabilize the G-quadruplex, but telomestatin appears much more selective, as shown by competition experiments with double-stranded DNA.
De Cian
Anne
A
Laboratoire de Biophysique, INSERM U565, CNRS UMR5153, Muséum National d'Histoire Naturelle, 43 rue Cuvier, 75005 Paris, France.
Guittat
Lionel
L
Shin-ya
Kazuo
K
Riou
Jean-François
JF
Mergny
Jean-Louis
JL
D004247:DNA / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D009691:Nucleic Acid Denaturation; D010080:Oxazoles / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011166:Porphyrins / Q000737:chemistry*; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000737:chemistry*
D004791:Enzyme Inhibitors; D008024:Ligands; D010080:Oxazoles; D011166:Porphyrins; C431888:telomestatin; C021096:tetra(4-N-methylpyridyl)porphine; D004247:DNA; D019098:Telomerase