Detection of G-quadruplex structures with a minimalistic crescent-shaped carbazole-indolium ligand

Abstract

G-quadruplexes (G4s) are non-canonical DNA or RNA secondary structures implicated in the regulation of some key biological processes like transcription and translation, which are now treated as promising therapeutic targets for many diseases. Although G4s have been studied for decades, the relationships between G4s (especially RNA G4s) and their cellular consequences remain largely unknown. Thus, development of promising fluorescent ligands that can detect G4 formation in live cells are urgently needed. Herein, we designed and synthesized a minimalistic, crescent-shaped carbazole-indolium conjugating ligand (KN-1), which was thus demonstrated to emit intense fluorescence upon interaction with G4s through a distinctive mode involved of end-stacking and groove-binding. Then, the behaviors of KN-1 in live cells were then investigated, illustrating that KN-1 could not only detect the RNA G4 formation but also stabilize the RNA G4 structures in live cells. Accordingly, this ligand may act as an applicable tool for monitoring RNA G4 formation and investigating the functions of specific RNA G4s in live cells.