Sequence-selective binding of C8-conjugated pyrrolobenzodiazepines (PBDs) to DNA
Sequence-selective binding of C8-conjugated pyrrolobenzodiazepines (PBDs) to DNA
DNA footprinting and melting experiments have been used to examine the sequence-specific binding of C8-conjugates of pyrrolobenzodiazepines (PBDs) and benzofused rings including benzothiophene and benzofuran, which are attached using pyrrole- or imidazole-containing linkers. The conjugates modulate the covalent attachment points of the PBDs, so that they bind best to guanines flanked by A/T-rich sequences on either the 5′- or 3′-side. The linker affects the binding, and pyrrole produces larger changes than imidazole. Melting studies with 14-mer oligonucleotide duplexes confirm covalent attachment of the conjugates, which show a different selectivity to anthramycin and reveal that more than one ligand molecule can bind to each duplex.
53-61
Basher, Mohammad
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Rahman, Khondakar M.
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Jackson, Paul J. M.
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Thurston, David E.
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Fox, Keith
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November 2017
Basher, Mohammad
936bf43e-dc1f-49a7-b445-65628e92d868
Rahman, Khondakar M.
daf186cd-2706-4f42-9ac0-28865f0518de
Jackson, Paul J. M.
a8f66bdd-98e9-43c7-b6c2-753659dc60e1
Thurston, David E.
9e2a56ac-259f-4977-a087-9d97c9003fbb
Fox, Keith
9da5debc-4e45-473e-ab8c-550d1104659f
Basher, Mohammad, Rahman, Khondakar M., Jackson, Paul J. M., Thurston, David E. and Fox, Keith
(2017)
Sequence-selective binding of C8-conjugated pyrrolobenzodiazepines (PBDs) to DNA.
Biophysical Chemistry, 230, .
(doi:10.1016/j.bpc.2017.08.006).
Abstract
DNA footprinting and melting experiments have been used to examine the sequence-specific binding of C8-conjugates of pyrrolobenzodiazepines (PBDs) and benzofused rings including benzothiophene and benzofuran, which are attached using pyrrole- or imidazole-containing linkers. The conjugates modulate the covalent attachment points of the PBDs, so that they bind best to guanines flanked by A/T-rich sequences on either the 5′- or 3′-side. The linker affects the binding, and pyrrole produces larger changes than imidazole. Melting studies with 14-mer oligonucleotide duplexes confirm covalent attachment of the conjugates, which show a different selectivity to anthramycin and reveal that more than one ligand molecule can bind to each duplex.
Text
PBD conjugates accepted
- Accepted Manuscript
More information
Accepted/In Press date: 18 August 2017
e-pub ahead of print date: 1 September 2017
Published date: November 2017
Identifiers
Local EPrints ID: 413870
URI: http://eprints.soton.ac.uk/id/eprint/413870
ISSN: 0301-4622
PURE UUID: 1d400b69-9c9d-4f13-a443-5e07e769d87b
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Date deposited: 08 Sep 2017 16:30
Last modified: 16 Mar 2024 05:42
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Contributors
Author:
Mohammad Basher
Author:
Khondakar M. Rahman
Author:
Paul J. M. Jackson
Author:
David E. Thurston
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