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  • Title: Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay.
    Author: Sheng Q, Neaverson JC, Mahmoud T, Stevenson CEM, Matthews SE, Waller ZAE.
    Journal: Org Biomol Chem; 2017 Jul 21; 15(27):5669-5673. PubMed ID: 28567459.
    Abstract:
    i-Motifs are quadruplex DNA structures formed from sequences rich in cytosine and held together by intercalated, hemi-protonated cytosine-cytosine base pairs. These sequences are prevalent in gene promoter regions and may play a role in gene transcription. Targeting these structures with ligands could provide a novel way to target genetic disease but there are very few ligands which have been shown to interact with i-motif DNA. Fluorescent intercalator displacement (FID) assays are a simple way to screen ligands against DNA secondary structures. Here we characterise how thiazole orange interacts with i-motif DNA and assess its ability for use in a FID assay. Additionally, we report FID-based ligand screening using thiazole orange against the i-motif forming sequence from the human telomere to reveal new i-motif binding compounds which have the potential for further development.
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