title: Surface-promoted aggregation of amphiphilic quadruplex ligands drives their selectivity for alternative DNA structures.
abstract: 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.
authors.affiliation: Institute of Molecular Chemistry, ICMUB CNRS UMR6302, Dijon, France. david.monchaud@cnrs.fr.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Laguerre
authors.forename: Yi
authors.initials: Y
authors.lastname: Chang
authors.forename: Marc
authors.initials: M
authors.lastname: Pirrotta
authors.forename: Nicolas
authors.initials: N
authors.lastname: Desbois
authors.forename: Claude P
authors.initials: CP
authors.lastname: Gros
authors.forename: Eric
authors.initials: E
authors.lastname: Lesniewska
authors.forename: David
authors.initials: D
authors.lastname: Monchaud
mesh_terms: D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D008024:Ligands; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D009690:Nucleic Acid Conformation; D011166:Porphyrins / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D008024:Ligands; D011166:Porphyrins; D013501:Surface-Active Agents; D004247:DNA