title: Nucleic acids targeted to drugs: SELEX against a quadruplex ligand.
abstract: A number of small molecules demonstrate selective recognition of G-quadruplexes and are able to stabilize their formation. In this work, we performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA by two complementary techniques, FRET and FID. The compound that exhibited the best characteristics (a biotin pyridocarboxamide derivative with high stabilization of an intramolecular quadruplex and excellent duplex-quadruplex specificity) was used as bait for in vitro selection (SELEX). Among 80 DNA aptamer sequences selected, only a small minority (5/80) exhibited G4-prone motifs. Binding of consensus candidates was confirmed by SPR. These results indicate that G4 ligands that appear highly specific when comparing affinities or stabilization for one quadruplex against one duplex, do not only bind quadruplex sequences but may also recognize other nucleic motifs as well. This observation may be relevant when whole genome or transcriptome analysis of binding sites is seeked for, as unexpected binding sites may also be present.
authors.affiliation: Université de Bordeaux, Laboratoire ARNA, Bordeaux, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Renaud de la Faverie
authors.forename: Florian
authors.initials: F
authors.lastname: Hamon
authors.forename: Carmelo
authors.initials: C
authors.lastname: Di Primo
authors.forename: Eric
authors.initials: E
authors.lastname: Largy
authors.forename: Eric
authors.initials: E
authors.lastname: Dausse
authors.forename: Laurence
authors.initials: L
authors.lastname: Delaurière
authors.forename: Corinne
authors.initials: C
authors.lastname: Landras-Guetta
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Toulmé
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mergny
mesh_terms: D001710:Biotin / Q000737:chemistry; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry; D015195:Drug Design; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D007364:Intercalating Agents / Q000737:chemistry; D008024:Ligands; D052156:SELEX Aptamer Technique; D020349:Surface Plasmon Resonance
chemical_list: D007364:Intercalating Agents; D008024:Ligands; D001710:Biotin; D003300:Copper