G-quadruplex recognition by quinacridines: a SAR, NMR, and biological study.
The synthesis of a novel group of quinacridine-based ligands (MMQs) is described along with an evaluation of their G-quadruplex binding properties. A set of biophysical assays was applied to characterize their interaction with DNA quadruplexes: FRET-melting experiments and equilibrium microdialysis were used to evaluate their quadruplex affinity and their ability to discriminate quadruplexes across a broad panel of DNA structures. All data collected support the proposed model of interaction of these compounds with G-quadruplexes, which is furthermore confirmed by a solution structure determined by 2D NMR experiments. Finally, the activity of the MMQ series against tumor cell growth is reported, and the data support the potential of quadruplex-interactive compounds for use in anticancer approaches.
Hounsou
Candide
C
Laboratoire de Chimie des Interactions Moléculaires, CNRS UPR 285, Collège de France, 11, place Marcellin Berthelot, 75005 Paris, France.
Guittat
Lionel
L
Monchaud
David
D
Jourdan
Muriel
M
Saettel
Nicolas
N
Mergny
Jean-Louis
JL
Teulade-Fichou
Marie-Paule
MP
D000166:Acridines / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship
D000166:Acridines