Journal
NATURE REVIEWS CHEMISTRY
Volume 1, Issue 5, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41570-017-0041
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Funding
- Pancreatic Cancer Research Fund
- Medical Research Council (UK)
- Wellcome Trust
- Johnson Johnson
- University College London Technology Fund
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Quadruplex nucleic acids-helical four-stranded structures known to form from guanine-rich nucleic acid sequences through Hoogsteen-type hydrogen bonding-were once just laboratory curiosities. However, they are now emerging from this rather obscure status to become important targets for small-molecule drugs, which can stabilize the quadruplex structures and thereby promote selective downregulation of gene expression and telomerase inhibition, and also activate DNA damage responses. Most of these quadruplex-binding small molecules can stabilize a range of cellular quadruplexes, as well as clusters of quadruplexes within a single gene or telomere, which could be an advantage. This widespread stabilization can generate a polygene response, and thus is able to simultaneously affect several key driver genes in human cancers, with potential therapeutic benefit.
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