Impact of planarity of unfused aromatic molecules on G-quadruplex binding: Learning from isaindigotone derivatives

摘要: G-quadruplex structures are a new class of attractive targets for DNA-interactive anticancer agents. The primary building block this structure is the G-quartet, which composed four coplanar guanines and serves as major binding site small molecules. NMR studies molecular dynamics simulations have suggested that planarity G-quartet surface has been highly dynamic in solution. To better investigate how unfused aromatic ligand impacts on its quadruplex properties, variety controllable isaindigotone derivatives were designed synthesized. interaction DNA with these ligands was systematically explored using series biophysical studies. FRET-melting, SPR, CD spectroscopy results showed reducing their core resulted decreased affinity stabilization ability G-quadruplex. also compounds could stack surface. Such parallel subsequent modeling A detailed energy analysis indicated van der Waals (ΔEvdw) entropy (TΔS) responsible effect. All provided insight information about recognition be controlled by adjusting ligands, shed light further development molecules optimal ligands.