G-Quadruplex-Based Fluorescent Turn-On Ligands and Aptamers: From Development to Applications

Abstract

Guanine (G)-quadruplexes (G4s) are unique nucleic acid structures that are formed by stacked G-tetrads in G-rich DNA or RNA sequences. G4s have been reported to play significant roles in various cellular events in both macro- and micro-organisms. The identification and characterization of G4s can help to understand their different biological roles and potential applications in diagnosis and therapy. In addition to biophysical and biochemical methods to interrogate G4 formation, G4 fluorescent turn-on ligands can be used to target and visualize G4 formation both in vitro and in cells. Here, we review several representative classes of G4 fluorescent turn-on ligands in terms of their interaction mechanism and application perspectives. Interestingly, G4 structures are commonly identified in DNA and RNA aptamers against targets that include proteins and small molecules, which can be utilized as G4 tools for diverse applications. We therefore also summarize the recent development of G4-containing aptamers and highlight their applications in biosensing, bioimaging, and therapy. Moreover, we discuss the current challenges and future perspectives of G4 fluorescent turn-on ligands and G4-containing aptamers.

A site-specific self-assembled light-up rotor probe for selective recognition and stabilization of c-MYC G-quadruplex DNA

“…8 and S20 †). [35][36][37] As expected, both Phen-DC 3 and PDS were able to fully displace 4b from the G-tetrad ends, highlighting the ability of 4b to target the G4 template via an endstacking binding mode. We observed a slightly different colour change in cuvette III (compare cuvettes marked as I with III, Fig.…”

Specific Binding of a d‐RNA G‐Quadruplex Structure with an l‐RNA Aptamer

“…Among all, the small‐molecule ligand is the major approach to detect G4 formation and interfere with G4‐mediated processes . While many G4‐specific ligands can distinguish G4s from other structural motifs, such as double/single‐stranded DNA/RNA, only a few have been reported to distinguish among G4s . Similarly, strategies using G4‐specific peptides or proteins to bind G4 have also been reported; however, so far limited cases have been demonstrated to have the potential to differentiate among G4s .…”

Spectroscopic Properties of Two 5′-(4-Dimethylamino)Azobenzene Conjugated G-Quadruplex Forming Oligonucleotides

“…Qs are often modified with suitable molecules in order to tune their stability or to provide them with specific properties such as fluorescence, chemical resistance, etc. [ 13 , 14 , 15 , 16 ]. Among the great number of molecules potentially appropriate for oligonucleotide (ON) modification, azobenzene and its derivatives, characterized by an extensive aromatic core, are of particular interest.…”