G-quadruplex Folding Modulation: Structural Insights, Selective Interaction, and Functional Activity

Dear Colleagues,

G-quadruplexes (G4s) are secondary structures of nucleic acids that contain stacked Hoogsteen H-bonded guanine quartets. These unusual four-stranded helixes have been visualized in human cells, and G4-prone motifs have been found in the genome of a massive range of organisms, including parasites, bacteria, viruses, and plants. The current understanding of the biological roles of G4s is mostly based on studying how biological macromolecules and synthetic small molecules modulate G4 folding in physiological environments. Several studies pointed out that there are different classes of proteins able to promote G4 folding and unfolding. Moreover, in the last decade, hundreds of small organic molecules have emerged for their ability to stabilize G4 structures and induce different biological responses. In this scenario, different ligands have emerged for their promising anticancer, antiviral, and antibacterial properties, highlighting that G4s represent a promising biological target regarding different pathologies. More recently, new molecular tools have been developed also to disrupt quadruplex structures in their native environment.

These experimental outcomes demonstrate that G4s are involved in several fundamental biological pathways, but, at the same time, underline the complexity of developing highly specific molecules and effective therapies. Off-target interactions and the still uncertain role of G4s in living organisms represent the main issue in the development of this research field. Therefore, further efforts should be dedicated to deeply investigating G4 structures and the mechanisms of interactions with other biomolecules in their native environments, and engineering new molecular tools to clarify their potential biological role and develop efficient ligands with well-defined biological responses. In this context, this Special Issue aims to promote original research, review articles, and commentaries focused on the correlation between the modulation of G4 structures and functional activity in the widest range of living organisms.

Dr. Valentina Pirota
Dr. Alessandra Benassi
Guest Editors

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• G-quadruplex
• G-quadruplex folding modulation
• G-quadruplex–molecule interactions
• biological processes regulation by G-quadruplex
• G4–protein interactions
• G4 ligands
• G4 covalent ligands
• RNA G-quadruplex