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Updated: Apr 11, 2026

Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
Surface-promoted aggregation of amphiphilic quadruplex ligands drives their selectivity for alternative DNA
Aurélien Laguerre1, Yi Chang, Marc Pirrotta
1Institute of Molecular Chemistry, ICMUB CNRS UMR6302, Dijon, France. david.monchaud@cnrs.fr.
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.
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