Tetrad-binding ligands do not bind specifically to left-handed G-quadruplexes

• Main Authors: Das, Poulomi, Phan, Anh Tuân
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Biological sciences; DNA; G-Quadruplexes
• Online Access: https://hdl.handle.net/10356/164741
• Institution: Nanyang Technological University

G-quadruplexes (G4s) are attractive anticancer targets. While right-handed G4s have been extensively investigated with many specific ligands reported, left-handed G4s formed by natural DNA have been recently discovered. Here we show that ligands specific for right-handed G4s, such as Phen-DC3 and RHAU peptide, do not bind specifically to left-handed G4s. In right-handed G4s, these ligands can displace capping overhangs and/or loops to stack on the exposed terminal tetrads. In contrast, the presence of tight T-capping in left-handed G4s hinders access to the tetrads.