title: Templated Formation of Discrete RNA and DNA:RNA Hybrid G-Quadruplexes and Their Interactions with Targeting Ligands.
abstract: G-rich RNA and DNA oligonucleotides derived from the human telomeric sequence were assembled onto addressable cyclopeptide platforms through oxime ligations and copper-catalyzed azide-alkyne cycloaddition (CuAAc) reactions. The resulting conjugates were able to fold into highly stable RNA and DNA:RNA hybrid G-quadruplex (G4) architectures as demonstrated by UV, circular dichroism (CD), and NMR spectroscopic analysis. Whereas rationally designed parallel RNA and DNA:RNA hybrid G4 topologies could be obtained, we could not force the formation of an antiparallel RNA G4 structure, thus supporting the idea that this topology is strongly disfavored. The binding affinities of four representative G4 ligands toward the discrete RNA and DNA:RNA hybrid G4 topologies were compared to the one obtained with the corresponding DNA G4 structure. Surface plasmon resonance (SPR) binding analysis suggests that the accessibility to G4 recognition elements is different among the three structures and supports the idea that G4 ligands might be shaped to achieve structure selectivity in a biological context.
authors.affiliation: Université Grenoble Alpes, Département de Chimie Moléculaire, UMR-5250, 38000, Grenoble, France.|CNRS, 38000, Grenoble, France.
authors.forename: Laureen
authors.initials: L
authors.lastname: Bonnat
authors.affiliation: Université Grenoble Alpes, Département de Chimie Moléculaire, UMR-5250, 38000, Grenoble, France.|CNRS, 38000, Grenoble, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dejeu
authors.affiliation: Université Grenoble Alpes, Département de Chimie Moléculaire, UMR-5250, 38000, Grenoble, France.|CNRS, 38000, Grenoble, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Bonnet
authors.affiliation: Université Grenoble Alpes, Département de Chimie Moléculaire, UMR-5250, 38000, Grenoble, France.|CNRS, 38000, Grenoble, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Génnaro
authors.affiliation: Université Grenoble Alpes, Département de Chimie Moléculaire, UMR-5250, 38000, Grenoble, France.|CNRS, 38000, Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Jarjayes
authors.affiliation: Université Grenoble Alpes, Département de Chimie Moléculaire, UMR-5250, 38000, Grenoble, France.|CNRS, 38000, Grenoble, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Thomas
authors.affiliation: Université Grenoble Alpes, Département de Chimie Moléculaire, UMR-5250, 38000, Grenoble, France. thomas.lavergne@ujf-grenoble.fr.|CNRS, 38000, Grenoble, France. thomas.lavergne@ujf-grenoble.fr.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-0029-0015
authors.initials: T
authors.lastname: Lavergne
authors.affiliation: Université Grenoble Alpes, Département de Chimie Moléculaire, UMR-5250, 38000, Grenoble, France. eric.defrancq@ujf-grenoble.fr.|CNRS, 38000, Grenoble, France. eric.defrancq@ujf-grenoble.fr.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0002-3911-6241
authors.initials: E
authors.lastname: Defrancq
mesh_terms: D001483:Base Sequence; D001686:Biological Phenomena; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009841:Oligonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*
chemical_list: D008024:Ligands; D009841:Oligonucleotides; D012313:RNA; D004247:DNA
keywords: DNA structures; G-quadruplexes; RNA structures; circular dichroism; click chemistry