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.

Highlights

  • Nucleic acids or the DNAs/RNAs contain the genetic information essential for life

  • Transition metal complexes incorporating several custom made ligands feature another class of well studied for G-quadruplex binding structures, which have shown a variety of applications, such as light switches, metal ion sensors etc.[78]

  • These results demonstrate that a small-molecule ligand such as carboxyPDS can target and trap RNA G-quadruplex structures selectively in the cytoplasm of human cells

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Summary

Introduction

Nucleic acids or the DNAs/RNAs contain the genetic information essential for life. In particular, their sequence encodes vital instructions for the cell, storage and replication of hereditary information.[1]. ChemComm to be potential drug targets, are examined for their interaction with small molecules[20] or metal ions, that can selectively affect its formation, recognize specific structures, and incorporate stimuli responsive fluorescence features All these contribute immensely towards the development of biosensors and anticancer therapeutics.[9,10,16,20]. The changes in the fluorescence behaviour of the dyes/ligands in the presence of a G-qudruplex have been utilized to visualize G-quadruplex formation in a human cell[11,28] and to detect metal ions[29,30,31,32] and small biomolecules such as amino acids, histidine (His), cysteine (Cys), biothiol,[33,34,35] in nanomolar range In this feature article we have overviewed some of the recent reports in this context and focus on the formation, stabilization, ligand binding of certain G-quadruplexes in the presence of biologically/technologically relevant small molecules and their prospective utilization as sensors for various applications

G-quadruplexes
Mechanistic insight into ligand binding
Extrinsic fluorogenic dyes with G-quadruplexes
Interaction of G-quadruplex with thioflavin T
Method
Interaction of G-quadruplex with porphyrins and phthalocyanines
Luminescent metal complexes
Visualization of a G-quadruplex in a human cell
Findings
Summary and outlook
Full Text
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