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Sequence-selective binding of C8-conjugated pyrrolobenzodiazepines (PBDs) to DNA

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.
0301-4622
53-61
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
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, 53-61. (doi:10.1016/j.bpc.2017.08.006).

Record type: Article

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.

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PBD conjugates accepted - Accepted Manuscript
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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
ORCID for Keith Fox: ORCID iD orcid.org/0000-0002-2925-7315

Catalogue record

Date deposited: 08 Sep 2017 16:30
Last modified: 17 Dec 2019 05:55

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Contributors

Author: Mohammad Basher
Author: Khondakar M. Rahman
Author: Paul J. M. Jackson
Author: David E. Thurston
Author: Keith Fox ORCID iD

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