Molecular Tools for Precision Targeting and Detection of G-Quadruplex Structures

In the context of the study of G-quadruplex (G4), the main field of focus is usually referred to binding molecules able to interact with these non-canonical conformations and stabilizing them leading to diverse biological effects. Although the cellular events triggered by these ligands are useful for potential anticancer applications, the development of innovative molecular tools to gain new information about G4 has become more urgent. The concept of G4-interacting molecular tools refers to chemical entities that can bind and interact with G-rich sequences of the genome—like traditional ligands—but simultaneously provide external outputs that can be interpreted and studied to obtain insights on their dynamics, position in the cellular context and more. Starting from traditional chemical approaches, researchers have worked to produce sophisticated and complex synthetic strategies in order to introduce more accurate instruments for their aims. This review provides a comprehensive and up-to-date overview of this research area by detailing the major classes of molecular tools, describing the latest updates about three main classes: small-molecules fluorescence probes, G4-binding metal complexes, and products of conjugation strategies. Overall, advancements in molecular tools targeting G4s have made the study of G4 formation, dynamics, and functions much easier; thus, increasing the knowledge of G4 biology, and creating new opportunities for biomedical and therapeutic applications, ultimately highlighting the importance of the development of molecular tools in G4 research.