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ChemMedChem. 2007 May;2(5):655-66.

G-quadruplex recognition by quinacridines: a SAR, NMR, and biological study.

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Laboratoire de Chimie des Interactions Mol├ęculaires, CNRS UPR 285, Coll├Ęge de France, 11, place Marcellin Berthelot, 75005 Paris, France.


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.

[Indexed for MEDLINE]

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