Interface of G-quadruplex with both stabilizing and destabilizing ligands for targeting various diseases

Abstract

Guanine-rich DNA sequences may fold back into non-canonical four-stranded secondary structures termed as G-quadruplexes. The role of G-quadruplexes has already been well established in different diseases like cancer, neurological and viral disorders etc. Also, several small molecules have been reported, which can influence the involvement of G-quadruplexes either through stabilization or destabilization in the cellular environment. Growing statistics have associated G-quadruplex assemblies to a discrete biological process in vivo, including DNA replication, transcription, genomic stability, and epigenetic regulation. DNA G-quadruplex existence in human telomere is well recognized attractive target for anticancer drugs. G-quadruplex-interactive ligands have been known to prevent telomerase access as well as telomere capping. To the best of our understanding, the role of G-quadruplexes in virology, neuropharmacology, cancer progression and its treatment has not been discussed on a single platform till date. This review aims to enhance our knowledge regarding these magical sticky quadruplex structures, which have been quite significantly proved to be the part of many cellular processes along with their established in vivo existence. Understanding regarding stabilizing or destabilizing ligands of these multistranded guanine quadruplex structures might be proved as the facilitator of drug discovery process for many incurable diseases in future.

Keywords: G-qaudruplex and SARS-Cov 2; G-quadruplex; G-quadruplex-ligand interaction; Guanine-rich DNA, G-quadruplex stabilizing ligands, G-quadruplex-destabilizing ligands; Neuropharmacology; Virology.