title: A twice-as-smart synthetic G-quartet: PyroTASQ is both a smart quadruplex ligand and a smart fluorescent probe.
abstract: 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.
authors.affiliation: Institute of Molecular Chemistry, University of Dijon, ICMUB CNRS UMR6302 , 21078 Dijon, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Laguerre
authors.forename: Loic
authors.initials: L
authors.lastname: Stefan
authors.forename: Manuel
authors.initials: M
authors.lastname: Larrouy
authors.forename: David
authors.initials: D
authors.lastname: Genest
authors.forename: Jana
authors.initials: J
authors.lastname: Novotna
authors.forename: Marc
authors.initials: M
authors.lastname: Pirrotta
authors.forename: David
authors.initials: D
authors.lastname: Monchaud
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000737:chemistry*; D054856:G-Quadruplexes; D008024:Ligands; D008958:Models, Molecular; D012313:RNA / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D012313:RNA; D004247:DNA