An estrogen-platinum terpyridine conjugate

DNA and protein binding and cellular delivery

Michael J. Hannon*, Philip S. Green, Dianne M. Fisher, Peter J. Derrick, Jennifer L. Beck, Stephen J. Watt, Stephen F. Ralph, Margaret M. Sheil, Philip R. Barker, Nathaniel W. Alcock, Robert J. Price, Karen J. Sanders, Richard Pither, Julie Davis, Alison Rodger

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

A platinum metal complex in which terpyridine joins estradiol (via an ethynyl link) to a platinum with a labile ligand (chloride) has been designed, synthesised and its X-ray crystal structure determined. The aim of this work was to link a targeting motif (in this case estrogen) to a metal-based biomolecule recognition unit (the platinum moiety). The target molecule: 17α-[4′-ethynyl-2,2′:6′,2′-terpyridine] -17β-estradiol platinum(II) chloride (PtEEtpy) has been shown to bind to both human and bovine serum albumin (SA) and to DNA. FTICR mass spectrometry shows that the bimolecular units are in each case linked through coordination to the platinum with displacement of the chloride ligand. Circular dichroism indicates that a termolecular entity involving PtEEtpy, SA and DNA is formed, A range of electrospray mass spectrometry experiments showed that the PtEEtpy complex breaks and forms coordination bonds relatively easily. A whole cell estrogen receptor assay in an estrogen receptor positive cell (MCF-7) confirms binding of both EEtpy and PtEEtpy to the estrogen receptor in cells. The work demonstrates the concept of linking a targeting moiety (in this case estrogen) to a DNA binding agent.

Original languageEnglish
Pages (from-to)8000-8013
Number of pages14
JournalChemistry - A European Journal
Volume12
Issue number31
DOIs
Publication statusPublished - 25 Oct 2006
Externally publishedYes

Keywords

  • Bioinorganic chemistry
  • DNA recognition
  • Steroid conjugates
  • Ternary complex
  • Terpyridines

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    Hannon, M. J., Green, P. S., Fisher, D. M., Derrick, P. J., Beck, J. L., Watt, S. J., ... Rodger, A. (2006). An estrogen-platinum terpyridine conjugate: DNA and protein binding and cellular delivery. Chemistry - A European Journal, 12(31), 8000-8013. https://doi.org/10.1002/chem.200501012