Identification of Three-Way DNA Junction Ligands through Screening of Chemical Libraries and Validation by Complementary in Vitro Assays

摘要: 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 these whose accumulation would result in damage through interference transactions transcription replication. Therefore, the chemical stabilization of offers an attractive way foster transaction-associated damages trigger cell death proliferating cancer cells. While much emphasis has been recently given quadruplexes, we focused here on three-way junctions (TWJ) report a strategy identify TWJ-targeting agents combination vitro techniques (TWJ-screen, polyacrylamide gel electrophoresis, fluorescence resonance energy transfer-melting, electrospray ionization mass spectrometry, dialysis equilibrium, sulforhodamine B assays). We designed complete workflow screened 1200 compounds promising TWJ ligands selected stringent criteria terms TWJ-folding ability, affinity, selectivity.