i-Motif DNA: Structure, stability and targeting with ligands

Henry A Day, Pavlos Pavlou, Zoë A E Waller

Research output: Contribution to journalArticlepeer-review

289 Citations (Scopus)


i-Motifs are four-stranded DNA secondary structures which can form in sequences rich in cytosine. Stabilised by acidic conditions, they are comprised of two parallel-stranded DNA duplexes held together in an antiparallel orientation by intercalated, cytosine-cytosine(+) base pairs. By virtue of their pH dependent folding, i-motif forming DNA sequences have been used extensively as pH switches for applications in nanotechnology. Initially, i-motifs were thought to be unstable at physiological pH, which precluded substantial biological investigation. However, recent advances have shown that this is not always the case and that i-motif stability is highly dependent on factors such as sequence and environmental conditions. In this review, we discuss some of the different i-motif structures investigated to date and the factors which affect their topology, stability and dynamics. Ligands which can interact with these structures are necessary to aid investigations into the potential biological functions of i-motif DNA and herein we review the existing i-motif ligands and give our perspective on the associated challenges with targeting this structure.
Original languageEnglish
Pages (from-to)4407–4418
Number of pages12
JournalBioorganic & Medicinal Chemistry
Issue number16
Early online date4 Jun 2014
Publication statusPublished - 15 Aug 2014


  • i-Motif
  • Cytosine
  • DNA secondary structure
  • G-quadruplex
  • DNA binding ligands

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