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Conjugation of testosterone modifies the interaction of mono-functional cationic platinum(II) complexes with DNA, causing significant alterations to the DNA helix

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Sanchez-Cano, Carlos, Huxley, Martin, Ducani, Cosimo, Hamad, Amal E., Browning, Michael J., Navarro-Ranninger, Carmen, Quiroga, Adoracion G., Rodger, Alison and Hannon, M. J.. (2010) Conjugation of testosterone modifies the interaction of mono-functional cationic platinum(II) complexes with DNA, causing significant alterations to the DNA helix. Dalton Transactions, Vol.39 (No.47). pp. 11365-11374. ISSN 1477-9226

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Official URL: http://dx.doi.org/10.1039/c0dt00839g

Abstract

Previously a range of androgen conjugates with non-conventional platinum(II) complexes have been synthesised with the aim of enhancing cellular delivery, and which have shown increased cytotoxic activity compared with non-steroidal compounds (M. J. Hannon et al., Dalton Trans., 2010, DOI: 10.1039/c0dt00838a). To further study this, the complexes have been assessed for their ability to bind to and alter the structure of DNA. All platinum(II) complexes studied herein bind to model nucleo-bases and DNA, but to our surprise, testosterone-based complexes caused the DNA helix to undergo significant unwinding and bending, whereas non-steroidal control complexes caused minimal structural alterations. These effects are similar to those cisplatin induces on DNA structure despite the fact that these compounds produce a monofunctional lesion. This ability attributed to interactions between the DNA helix and bulky steroidal skeleton of testosterone, coupled with the enhanced cellular delivery induced by the steroid make the steroid approach an exciting way to explore non-conventional platinum drug delivery.

Item Type:

Journal Article

Subjects:

Q Science > QD Chemistry
Q Science > QP Physiology

Divisions:

Faculty of Science > Chemistry

Library of Congress Subject Headings (LCSH):

Bioconjugates, Testosterone, Metal complexes, Platinum, Drug delivery systems, DNA

Journal or Publication Title:

Dalton Transactions

Publisher:

Royal Society of Chemistry

ISSN:

1477-9226

Official Date:

21 December 2010

Dates:

Date	Event
21 December 2010	Published

Volume:

Vol.39

Number:

No.47

Number of Pages:

Page Range:

pp. 11365-11374

Identification Number:

10.1039/c0dt00839g

Status:

Peer Reviewed

Publication Status:

Published

Access rights to Published version:

Restricted or Subscription Access

Funder:

Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University of Birmingham, University of Warwick, European Union, Spain. Comisión Interministerial de Ciencia y Tecnología (CICYT)

Grant number:

SAF 2006-03296 (CICYT), SAF 2009-0431 (CICYT)

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