Targeting G-quadruplex structures with extrinsic fluorogenic dyes: promising fluorescence sensors

Abstract

The research on the G-quadruplex DNAs has received much attention in recent years and numerous reports appeared probing their detection, structure, stability, reactivity, selectivity, etc. for the chemical intervention of their biological activity or sensor applications. This feature article provides an account of the recent reports from different research groups on the intriguing fluorescence properties showcased by certain fluorogenic dyes upon their binding to the G-quadruplex DNAs. Aptly, these selective and sensitive emission features demonstrated with structure specific G-quadruplex DNAs have been turned into label-free fluorescence-based detection methods for various metal ions and small biomolecules, down to the pico molar range, having promising bio-analytical applications. While the in vivo formation of G-quadruplexes is dynamically sensitive to the cell cycle, in tandem with the in vitro applications, it is essential to understand the factors that affect chemical, biological and genetic roles of the G-quadruplex structures plausible along the human genome. Towards this, the recent findings on the quantitative visualization of the quadruplex structures in the human cells using immunofluorescent probes open up avenues to explore highly specific quadruplex responsive agents for diagnostic and therapeutic applications, especially to develop a clinically viable method for cancer treatment.

Development of squaraine based G-quadruplex ligands using click chemistry

“…Guanine-rich nucleic acids (DNA or RNA) are known to self-assemble into four-stranded structures defined as G-quadruplexes (G4s), which are composed of the planar arrangement of four guanine bases stabilized by Hoogsteen hydrogen bonds (known as a G-quartet) 1–3 . Such G4 forming sequences have been reported to be prevalent in genomes, such as immunoglobulin switch regions and promoter regions of oncogenes and telomere ends 4, 5 , as well as in particular RNA domains, such as the first introns, 5′- and 3′- untranslated regions, telomeric RNA 6 , and the genomic RNA of Zika virus replication 7 .…”

“…Therefore, in recent years, the development of G4 ligands as chemotherapy agents or detection probes has attracted a substantial amount of effort 3, 15–22 . Arising from these studies are a wide variety of G4 ligand variants, such as acridine derivatives, bisquinolinium derivatives, cationic porphyrins, ethidium derivatives, triarylimidazole derivatives and transition metal complexes 2, 23–34 .…”

Label‐free molecular probe based on G‐quadruplex and strand displacement for sensitive and selective detection and naked eye discrimination of exon 2 deletion of AIMP2

“…Among these methods, label‐free fluorescent biosensors received intense attention with the advantages of easy‐operating, cost‐effective and time‐saving . For example, N ‐methyl mesoporphyrin IX (NMM), an unsymmetrical anionic porphyrin which could specifically bind to G‐quadruplex and generate a dramatic fluorescence increase has been used to construct label‐free biosensors for the detection of different targets . Furthermore, hemin can bind to G‐quadruplex and then constitute a horseradish peroxidase‐mimicking DNAzyme, which can catalyse H 2 O 2 to oxidize colourless 2,2′‐azino‐bis (3‐ethylbenzothiazo‐line)‐6‐sulfonate disodium salt (ABTS 2− ) to green ABTS ·− .…”

Combining a Ru(II) “Building Block” and Rapid Screening Approach to Identify DNA Structure-Selective “Light Switch” Compounds

“…13 Certain DNA defects and structures are more prevalent in human diseases, and the design of molecules with increasingly selective DNA recognition is an active area in drug discovery research. 7, 16–21 Two important goals involve identifying molecules that luminesce upon binding to specific DNA sequences or structures 22–26 and assay development for rapid identification of compounds that selectively bind biologically relevant DNA targets. 27 …”