title: Screening of a chemical library by HT-G4-FID for discovery of selective G-quadruplex binders.
abstract: Due to the lack of structural guidelines about G-quadruplex ligands, rational design cannot be the only approach to discover potent G4-ligands. As a complementary approach, screening of chemical library may provide interesting scaffolds known as hits provided that specific tools are available. In this work, the Institut Curie-CNRS chemical library was firstly screened by chemoinformatics methods. Similarity estimations by comparison with reference compounds (Phen-DC3, 360A, MMQ12) provided a set of molecules, which were then evaluated by high-throughput G4-FID (HT-G4-FID) against various G-quadruplex DNA. A full investigation of the most interesting molecules, using the HT-G4-FID assay and molecular modeling, supplied an interesting structure-activity relationship confirming the efficiency of this general approach. Overall, we demonstrated that HT-G4-FID coupled with screening of chemical libraries is a powerful tool to identify new G4-DNA binding scaffolds.
authors.affiliation: Institut Curie, Centre Universitaire, Orsay, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Largy
authors.forename: Nicolas
authors.initials: N
authors.lastname: Saettel
authors.forename: Florian
authors.initials: F
authors.lastname: Hamon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dubruille
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
mesh_terms: D004247:DNA / Q000737:chemistry*; D055808:Drug Discovery; D054856:G-Quadruplexes; D057166:High-Throughput Screening Assays / Q000379:methods*; D007364:Intercalating Agents / Q000737:chemistry*; D008024:Ligands; D054852:Small Molecule Libraries / Q000032:analysis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D007364:Intercalating Agents; D008024:Ligands; D054852:Small Molecule Libraries; D004247:DNA