Zhujun Ma
An organometallic compound which exhibits a DNA topology-dependent one-stranded intercalation mode
Ma, Zhujun; Palermo, Giulia; Adhireksan, Zenita; Murray, Benjamin S.; von Erlach, Thibaud; Dyson, Paul J.; Rothlisberger, Ursula; Davey, Curt A.
Authors
Giulia Palermo
Zenita Adhireksan
Benjamin S. Murray
Thibaud von Erlach
Paul J. Dyson
Ursula Rothlisberger
Curt A. Davey
Abstract
Understanding how small molecules interact with DNA is essential since it underlies a multitude of pathological conditions and therapeutic interventions. Many different intercalator compounds have been studied because of their activity as mutagens or drugs, but little is known regarding their interaction with nucleosomes, the protein-packaged form of DNA in cells. Here, using crystallographic methods and molecular dynamics simulations, we discovered that adducts formed by [(η⁶-THA)Ru(ethylenediamine)Cl][PF₆] (THA = 5,8,9,10-tetrahydroanthracene; RAED-THA-Cl[PF₆]) in the nucleosome comprise a novel one-stranded intercalation and DNA distortion mode. Conversely, the THA group in fact remains solvent exposed and does not disrupt base stacking in RAED-THA adducts on B-form DNA. This newly observed DNA binding mode and topology dependence may actually be prevalent and should be considered when studying covalently binding intercalating compounds.
Citation
Ma, Z., Palermo, G., Adhireksan, Z., Murray, B. S., von Erlach, T., Dyson, P. J., Rothlisberger, U., & Davey, C. A. (2016). An organometallic compound which exhibits a DNA topology-dependent one-stranded intercalation mode. Angewandte Chemie, 128(26), 7567-7570. https://doi.org/10.1002/ange.201602145
Journal Article Type | Article |
---|---|
Acceptance Date | Apr 19, 2016 |
Online Publication Date | May 13, 2016 |
Publication Date | Jun 20, 2016 |
Deposit Date | Jun 8, 2016 |
Publicly Available Date | Jun 8, 2016 |
Journal | Angewandte Chemie |
Print ISSN | 1433-7851 |
Publisher | Wiley |
Peer Reviewed | Peer Reviewed |
Volume | 128 |
Issue | 26 |
Pages | 7567-7570 |
DOI | https://doi.org/10.1002/ange.201602145 |
Keywords | Anti-cancer agents, DNA adducts, Intercalators, Molecular dynamics, Organometallic compounds |
Public URL | https://hull-repository.worktribe.com/output/439249 |
Publisher URL | http://onlinelibrary.wiley.com/doi/10.1002/ange.201602145/full |
Additional Information | Authors' accepted manuscript of article published in: Angewandte Chemie, 2016, v.128, issue 26. |
Contract Date | Jun 8, 2016 |
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©2017 University of Hull
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