Surface-promoted aggregation of amphiphilic quadruplex ligands drives their selectivity for alternative DNA structures.
Fiche publication
Date publication
juillet 2015
Journal
Organic & biomolecular chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MONCHAUD David
Tous les auteurs :
Laguerre A, Chang Y, Pirrotta M, Desbois N, Gros CP, Lesniewska E, Monchaud D
Lien Pubmed
Résumé
Scientists are currently truly committed to enhance the specificity of chemotherapeutics that target DNA. To this end, sequence-specific drugs have progressively given way to structure-specific therapeutics. However, while numerous strategies have been implemented to design high-affinity candidates, strategies devoted to the design of high-selectivity ligands are still rare. Here we report on such an approach via the study of an amphiphilic compound, TEGPy, that self-assembles at a liquid/solid interface to provide nanosized objects that are stable in water. The resulting aggregates, identified through atomic force microscopy measurements, were found to disassemble upon interaction with DNA in a structure-specific manner (quadruplex- versus duplex-DNA). Our results provide a fertile ground for devising new strategies aiming at concomitantly enhancing DNA structural specificity and the water-solubility of aggregation-prone ligands.
Mots clés
DNA, chemistry, G-Quadruplexes, Ligands, Microscopy, Atomic Force, Models, Molecular, Nanostructures, chemistry, Nucleic Acid Conformation, Porphyrins, chemistry, Surface-Active Agents, chemistry
Référence
Org. Biomol. Chem.. 2015 Jul 7;13(25):7034-9