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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

Zhujun Ma

Giulia Palermo

Zenita Adhireksan

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., …Davey, C. A. (2016). An organometallic compound which exhibits a DNA topology-dependent one-stranded intercalation mode. Angewandte Chemie, 128(26), 7567-7570. doi: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
Electronic ISSN 1521-3757
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
Copyright Statement ©2017 University of Hull
Additional Information Authors' accepted manuscript of article published in: Angewandte Chemie, 2016, v.128, issue 26.

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