Molecular engineering of a near-infrared fluorescent ligand for tracking mitochondrial DNA G-quadruplexes

Abstract

G-quadruplexes are supposed to exist in mitochondrial DNA, which may participate in the regulation of mitochondrial metabolism. However, their formation dynamics and cellular roles are still unknown, calling for the development of promising small-molecule fluorescent probes for detecting mitochondrial DNA (mtDNA) G4s in live cells. In this study, we engineered a NIR fluorescent probe termed IZIN-1 by conjugating a typical G4 ligand and a mitochondrion-targeting AIE luminogen, which was then found to be able to emit NIR fluorescence by binding to mtDNA G4s via a distinctive mode. Cell-based experiments demonstrated that IZIN-1 may track mtDNA G4 formation in live cells. Collectively, this work provides a promising example about how to design a fluorescent probe targeting mtDNA G4s, and also offers a feasible chemical tool for investigating mtDNA G4s in live cells.

Keywords: Engineering; Fluorescent; G-quadruplex; Mitochondria; Near-infrared.