G-quadruplex structure (G4)

G-quadruplex structures (G4s) are noncanonical four-stranded secondary structures formed by guanine-rich DNA or RNA sequences through the stacking of guanine tetrads (G-quartets) stabilized by Hoogsteen hydrogen bonds and central monovalent cations, usually potassium. G-quadruplexes are found in telomeres and regulatory gene regions across species, where they play critical roles in the regulation of transcription, replication, telomere maintenance, and genome stability. They can regulate gene expression, serve as roadblocks to polymerases, and are implicated in diverse diseases, especially cancer, due to their prevalence at oncogene promoters and telomeric regions. Summoning increasing interest as therapeutic targets, small molecules that selectively bind and stabilize or destabilize G4s are being developed as potential anti-cancer agents. The broad distribution and fundamental genome-wide roles of G4s pose challenges to their therapeutic targeting, with safety concerns stemming from potential disruption of essential cellular processes and genome integrity.

Other names

G-quadruplexG4guanine quadruplexG-quartettetraplex (not recommended)

Stabilization of G-quadruplex structures in DNA/RNA, thereby modulating gene transcription or telomerase activity; Inhibition of replication or transcriptional machinery at G4-rich regions; Disruption of telomere maintenance by preventing telomerase access