Binding and beyond: what else can G-quadruplex ligands do?

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G-quadruplexes (G4) are four-stranded structures formed from guanine-rich oligonucleotides. Their defined 3D structures and polymorphic nature set them apart from classical nucleic acid morphology and suggest a range of potential applications in the development of functional materials. Meanwhile, the occurrence of G4 across the genomes of animals, plants and pathogens suggests roles for these structures in biology that may be exploited for therapeutic effect. Hundreds of G4 ligands are reported to bind these sequences with high specificity and affinity, but such ligands can also be engineered to do more than simply associate with G4 in a straightforward host-guest fashion. Ligands have been developed that can switch G4 topology, direct the selective covalent modification of nucleic acid structures, or respond to external stimuli to permit spatiotemoral control of their activity. Herein we survey the main themes of such “value-added” G4 ligands and consider the opportunities and challenges of their potential applications.
Original languageEnglish
Number of pages24
JournalEuropean Journal of Organic Chemistry
Early online date5 Jul 2019
Publication statusE-pub ahead of print - 5 Jul 2019

Structured keywords

  • BCS and TECS CDTs


  • supramolecular chemistry
  • RNA
  • nucleic acids
  • G-quadruplexes
  • DNA

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