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Issue 27, 2017
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Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay

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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.

Graphical abstract: Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay

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Article information


Submitted
22 Mar 2017
Accepted
22 May 2017
First published
01 Jun 2017

This article is Open Access

Org. Biomol. Chem., 2017,15, 5669-5673
Article type
Communication

Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay

Q. Sheng, J. C. Neaverson, T. Mahmoud, C. E. M. Stevenson, S. E. Matthews and Z. A. E. Waller, Org. Biomol. Chem., 2017, 15, 5669
DOI: 10.1039/C7OB00710H

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