Wilson, T, Costa, P.J, Felix, V et al. (2 more authors) (2013) Structural Studies on Dinuclear Ruthenium(II) Complexes That Bind Diastereoselectively to an Antiparallel Folded Human Telomere Sequence. Journal of Medicinal Chemistry, 56 (21). 8674 - 8683. ISSN 0022-2623
Abstract
We report DNA binding studies of the dinuclear ruthenium ligand [{Ru(phen)2}2tpphz]4+ in enantiomerically pure forms. As expected from previous studies of related complexes, both isomers bind with similar affinity to BDNA and have enhanced luminescence. However, when tested against the G-quadruplex from human telomeres (which we show to form an antiparallel basket structure with a diagonal loop across one end), the ΛΛ isomer binds approximately 40 times more tightly than the ΔΔ, with a stronger luminescence. NMR studies show that the complex binds at both ends of the quadruplex. Modeling studies, based on experimentally derived restraints obtained for the closely related [{Ru(bipy)2}2tpphz]4+, show that the ΛΛ isomer fits neatly under the diagonal loop, whereas the ΔΔ isomer is unable to bind here and binds at the lateral loop end. Molecular dynamics simulations show that the ΔΔ isomer is prevented from binding under the diagonal loop by the rigidity of the loop. We thus present a novel enantioselective binding substrate for antiparallel basket G-quadruplexes, with features that make it a useful tool for quadruplex studies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 American Chemical Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Funding Information: | Funder Grant number EPSRC EP/C512855/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 May 2014 13:30 |
Last Modified: | 08 May 2014 13:30 |
Published Version: | http://dx.doi.org/10.1021/jm401119b |
Status: | Published |
Publisher: | American Chemical Society |
Refereed: | Yes |
Identification Number: | 10.1021/jm401119b |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:78866 |