Duskova K Lamarche J Amor S Caron C Queyriaux N Gaschard M Penouilh MJ de Robillard G Delmas D Devillers CH Granzhan A Teulade-Fichou MP Chavarot-Kerlidou M Therrien B Britton S Monchaud D 2019 The human genome is replete with repetitive DNA sequences that can fold into thermodynamically stable secondary structures such as hairpins and quadruplexes. Cellular enzymes exist to cope with these structures whose stable accumulation would result in DNA damage through interference with DNA transactions such as transcription and replication. Therefore, the chemical stabilization of secondary DNA structures offers an attractive way to foster DNA transaction-associated damages to trigger cell death in proliferating cancer cells. While much emphasis has been recently given to DNA quadruplexes, we focused here on three-way DNA junctions (TWJ) and report on a strategy to identify TWJ-targeting agents through a combination of in vitro techniques (TWJ-screen, polyacrylamide gel electrophoresis, fluorescence resonance energy transfer-melting, electrospray ionization mass spectrometry, dialysis equilibrium, and sulforhodamine B assays). We designed a complete workflow and screened 1200 compounds to identify promising TWJ ligands selected on stringent criteria in terms of TWJ-folding ability, affinity, and selectivity. application/pdf https://sonar.ch/global/documents/139951 eng info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jmedchem.8b01978 info:eu-repo/semantics/altIdentifier/pmid/30942581 info:eu-repo/semantics/openAccess Journal of medicinal chemistry. - 2019 Antineoplastic Agents Cell Line, Tumor Cell Proliferation DNA Electrophoresis, Polyacrylamide Gel Fluorescence Resonance Energy Transfer Humans Ligands Nucleic Acid Conformation Small Molecule Libraries Spectrometry, Mass, Electrospray Ionization Identification of Three-Way DNA Junction Ligands through Screening of Chemical Libraries and Validation by Complementary in Vitro Assays. http://purl.org/coar/resource_type/c_6501