DNA binding by analogues of the bifunctional intercalator TANDEM

Hampshire, Andrew J., Rusling, David A., Bryan, Stephanie, Paumier, David, Dawson, Simon J., Malkinson, John P., Searcey, Mark ORCID: https://orcid.org/0000-0003-2273-8949 and Fox, Keith R. (2008) DNA binding by analogues of the bifunctional intercalator TANDEM. Biochemistry, 47 (30). pp. 7900-7906.

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We have used DNase I footprinting to study the binding strength and DNA sequence selectivity of novel derivatives of the quinoxaline bis-intercalator TANDEM. Replacing the valine residues in the cyclic octadepsipeptide with lysines does not affect the selectivity for TpA but leads to a 50-fold increase in affinity. In contrast, replacing both of the quinoxaline chromophores with naphthalene rings abolishes binding, while changing a single ring decreases the affinity, and footprints are observed at only the best binding sites (especially TATATA). By using fragments with different lengths of [(AT)n], we demonstrate that these ligands bind best to the center of the longer (AT)n tracts.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Rachel Smith
Date Deposited: 17 Mar 2011 14:21
Last Modified: 12 Jan 2023 17:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/26560
DOI: 10.1021/bi800573p

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