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.
Highlights
Guanine (G)-rich sequences in nucleic acids have the potential to fold into structural motifs referred to as G-quadruplexes (G4s)
We summarize the recent development of fluorogenic G4 ligands and G4-containing aptamers, and highlight their latest applications in vitro and in cells (Figure 1D)
We focus on crystal violet (CV) and malachite green (MG)
Summary
Guanine (G)-rich sequences in nucleic acids have the potential to fold into structural motifs referred to as G-quadruplexes (G4s). Mapper [20], quadparser [3], G4 Hunter [21], G4NN [22], and Quadron [23] have been developed to predict G4 formations Spectroscopic techniques such as circular dichroism (CD) [24], UV melting [25], mass spectrometry [26], nuclear magnetic resonance (NMR) [27], and intrinsic fluorescence [28] can detect G4 formation based on its physical properties in a label-free manner.
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