title: Cationic pentaheteroaryls as selective G-quadruplex ligands by solvent-free microwave-assisted synthesis.
abstract: We report herein a solvent-free and microwaved-assisted synthesis of several water soluble acyclic pentaheteroaryls containing 1,2,4-oxadiazole moieties (1-7). Their binding interactions with DNA quadruplex structures were thoroughly investigated by FRET melting, fluorescent intercalator displacement assay (G4-FID) and CD spectroscopy. Among the G-quadruplexes considered, attention was focused on telomeric repeats together with the proto-oncogenic c-kit sequences and the c-myc oncogene promoter. Compound 1, and to a lesser extent 2 and 5, preferentially stabilise an antiparallel structure of the telomeric DNA motif, and exhibit an opposite binding behaviour to structurally related polyoxazole (TOxaPy), and do not bind duplex DNA. The efficiency and selectivity of the binding process was remarkably controlled by the structure of the solubilising moieties.
authors.affiliation: Dipartimento di Chimica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Petenzi
authors.forename: Daniela
authors.initials: D
authors.lastname: Verga
authors.forename: Eric
authors.initials: E
authors.lastname: Largy
authors.forename: Florian
authors.initials: F
authors.lastname: Hamon
authors.forename: Filippo
authors.initials: F
authors.lastname: Doria
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.forename: Aurore
authors.initials: A
authors.lastname: Guédin
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mergny
authors.forename: Mariella
authors.initials: M
authors.lastname: Mella
authors.forename: Mauro
authors.initials: M
authors.lastname: Freccero
mesh_terms: D002412:Cations / Q000737:chemistry; D002942:Circular Dichroism; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000737:chemistry; D054856:G-Quadruplexes; D008024:Ligands; D008872:Microwaves; D010069:Oxadiazoles / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D002412:Cations; D005456:Fluorescent Dyes; D008024:Ligands; D010069:Oxadiazoles; D014867:Water