DNA binding by analogues of the bifunctional intercalator TANDEM
DNA binding by analogues of the bifunctional intercalator TANDEM
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.
7900-7906
Hampshire, Andrew J.
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Rusling, David A.
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Bryan, Stephanie
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Paumier, David
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Dawson, Simon J.
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Malkinson, John P.
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Searcey, Mark
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Fox, Keith R.
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29 July 2008
Hampshire, Andrew J.
68aac3b7-88b7-4417-8793-9c2a06b01abc
Rusling, David A.
d08f1f97-f8a9-4980-a025-ae41c23a938f
Bryan, Stephanie
8c195aed-24d0-465c-b689-e08a5b76c591
Paumier, David
73b2a6fe-881e-43f8-9bfd-e33a1d82a665
Dawson, Simon J.
b4f4fc55-7c16-467b-88d6-5754e172c87a
Malkinson, John P.
a8f447bf-dc3e-48f6-8129-8aebd348ee73
Searcey, Mark
92a85b46-a185-4c99-b12d-0e763be6549e
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Hampshire, Andrew J., Rusling, David A., Bryan, Stephanie, Paumier, David, Dawson, Simon J., Malkinson, John P., Searcey, Mark and Fox, Keith R.
(2008)
DNA binding by analogues of the bifunctional intercalator TANDEM.
Biochemistry, 47 (30), .
(doi:10.1021/bi800573p).
(PMID:18597492)
Abstract
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.
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Published date: 29 July 2008
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Local EPrints ID: 142573
URI: http://eprints.soton.ac.uk/id/eprint/142573
ISSN: 0006-2960
PURE UUID: f45566ae-6072-4867-88d9-b6c007b655b2
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Date deposited: 01 Apr 2010 15:42
Last modified: 14 Mar 2024 02:33
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Author:
Andrew J. Hampshire
Author:
David A. Rusling
Author:
Stephanie Bryan
Author:
David Paumier
Author:
Simon J. Dawson
Author:
John P. Malkinson
Author:
Mark Searcey
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