Fiche publication
Date publication
septembre 2014
Journal
Journal of the American Chemical Society
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MONCHAUD David
Tous les auteurs :
Laguerre A, Stefan L, Larrouy M, Genest D, Novotna J, Pirrotta M, Monchaud D
Lien Pubmed
Résumé
Recent and unambiguous evidences of the formation of DNA and RNA G-quadruplexes in cells has provided solid support for these structures to be considered as valuable targets in oncology. Beyond this, they have lent further credence to the anticancer strategies relying on small molecules that selectively target these higher-order DNA/RNA architectures, referred to as G-quadruplex ligands. They have also shed bright light on the necessity of designing multitasking ligands, displaying not only enticing quadruplex interacting properties (affinity, structural selectivity) but also additional features that make them usable for detecting quadruplexes in living cells, notably for determining whether, when, and where these structures fold and unfold during the cell cycle and also for better assessing the consequences of their stabilization by external agents. Herein, we report a brand new design of such multitasking ligands, whose structure experiences a quadruplex-promoted conformational switch that triggers not only its quadruplex affinity (i.e., smart ligands, which display high affinity and selectivity for DNA/RNA quadruplexes) but also its fluorescence (i.e., smart probes, which behave as selective light-up fluorescent reporters on the basis of a fluorogenic electron redistribution). The first prototype of such multifunctional ligands, termed PyroTASQ, represents a brand new generation of quadruplex ligands that can be referred to as "twice-as-smart" quadruplex ligands.
Mots clés
Base Sequence, DNA, chemistry, Fluorescence Resonance Energy Transfer, Fluorescent Dyes, chemistry, G-Quadruplexes, Ligands, Models, Molecular, RNA, chemistry
Référence
J. Am. Chem. Soc.. 2014 Sep 3;136(35):12406-14
