Effects of Fluorine Substitution on the Human Telomeric RNA G-Quadruplex Structure

DNA G-quadruplex structures can adopt different topologies, whereas RNA G4 predominantly forms parallel-type structures. While previous studies have reported the stabilization of DNA G-quadruplex topologies using syn-favored nucleosides, stabilization of parallel-type RNA G-quadruplexes through chemical modification remains unachieved. Here, we demonstrate that substitution with 2'-deoxy-2'-fluoroarabinoguanosine (2'F-araG) at specific positions in the human telomeric RNA sequence stabilizes the parallel-type G-quadruplex structure. This stabilization arises from electrostatic interactions via pseudo hydrogen bonds, induced by the 2'F-araG modification.