Genomic and RNA G-quadruplex structures (G4) (G4)

G-quadruplexes (G4s) are non-canonical secondary structures formed by guanine-rich sequences in DNA and RNA, characterized by the stacking of G-tetrads stabilized by Hoogsteen base pairing and monovalent cations (Source: Nature Reviews Drug Discovery, PMID: 21681191). These structures are prevalent in key regulatory regions of the genome, including telomeres and the promoters of potent oncogenes such as c-MYC, KRAS, and BCL-2, as well as in the 5' untranslated regions of mRNA (Source: PubMed, PMID: 30104617). In a biological context, G4s act as molecular switches that regulate critical processes like gene transcription, mRNA translation, and DNA replication (Source: Nucleic Acids Research, PMID: 32411315). Their enrichment in cancer cells and association with genomic instability make them attractive therapeutic targets for oncology and other diseases. Small molecules designed to stabilize G4 structures can selectively inhibit the expression of oncogenes or disrupt telomere maintenance, leading to cell cycle arrest and apoptosis in malignant cells (Source: Journal of Medicinal Chemistry, PMID: 28252971). Beyond cancer, G4s are implicated in neurodegenerative diseases, such as ALS and FTD, where they form in repeat expansion sequences like C9orf72 (Source: Nature Communications, PMID: 25732150). They also play roles in viral life cycles, making them potential targets for antiviral therapy (Source: Chemical Reviews, PMID: 32809831). However, the ubiquitous nature of G4-forming sequences across the genome presents significant challenges regarding selectivity and potential off-target toxicity (Source: Trends in Pharmacological Sciences, PMID: 25455237).

Other names

G-quadruplexesG4-DNAG4-RNAG-tetraplexesG-clustersG-rich sequences

Stabilization of G-quadruplex structures to inhibit transcription of oncogenes (e.g., c-MYC, KRAS), interfere with telomere maintenance, or block translation of viral and oncogenic mRNA.