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

Sheng, Qiran, Neaverson, Joseph C., Mahmoud, Tasnim, Stevenson, Clare E. M., Matthews, Susan E. ORCID: https://orcid.org/0000-0001-8821-0851 and Waller, Zoë A. E. (2017) Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay. Organic & Biomolecular Chemistry, 15 (27). pp. 5669-5673. ISSN 1477-0520

[thumbnail of Published manuscript]
Preview
PDF (Published manuscript) - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

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.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Pharmacy (former - to 2024)
Faculty of Science > School of Biological Sciences
Faculty of Science > School of Natural Sciences (former - to 2024)
UEA Research Groups: Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017)
Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
Related URLs:
Depositing User: Pure Connector
Date Deposited: 28 Jul 2017 05:06
Last Modified: 15 Oct 2024 00:16
URI: https://ueaeprints.uea.ac.uk/id/eprint/64286
DOI: 10.1039/C7OB00710H

Downloads

Downloads per month over past year

Actions (login required)

View Item View Item