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JBIC Journal of Biological Inorganic Chemistry

, Volume 12, Issue 8, pp 1107–1117 | Cite as

Ruthenium anticancer drugs and proteins: a study of the interactions of the ruthenium(III) complex imidazolium trans-[tetrachloro(dimethyl sulfoxide)(imidazole)ruthenate(III)] with hen egg white lysozyme and horse heart cytochrome c

  • Angela Casini
  • Guido Mastrobuoni
  • Mattia Terenghi
  • Chiara Gabbiani
  • Enrico Monzani
  • Gloriano Moneti
  • Luigi Casella
  • Luigi MessoriEmail author
Original Paper

Abstract

The interactions with protein targets of the ruthenium(III) complex imidazolium trans-[tetrachloro(dimethyl sulfoxide)(imidazole)ruthenate(III)], NAMI-A, an effective anticancer and antimetastatic agent now in clinical trials, deserve great attention as they are believed to be at the basis of the mechanism of action of this innovative molecule. Here, we report on the reactions of NAMI-A with two well-known model proteins, namely, hen egg white lysozyme and horse heart cytochrome c; these reactions were investigated by a variety of physicochemical methods, including optical spectroscopy, 1H NMR and electrospray ionization mass spectrometry. The combined use of the analytical techniques mentioned resulted in a rather exhaustive description of the NAMI-A–protein interactions; in particular, the formation of fairly stable metal–protein adducts was clearly documented and the nature of the resulting protein-bound metallic fragments ascertained in most cases. Notably, greatly different patterns of interaction were found to be operative for NAMI-A toward these two proteins. The biological implications of the present findings are discussed.

Keywords

Ruthenium metal complexes Cancer Proteins NMR Electrospray ionization mass spectrometry 

Notes

Acknowledgements

CIRCMSB, MIUR, and Ente Cassa di Risparmio di Firenze are gratefully acknowledged for financial support. We thank AIRC for a grant to A.C. Scientific discussion with Enzo Alessio on the main aspects of this study turned out to be very illuminating.

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Copyright information

© SBIC 2007

Authors and Affiliations

  • Angela Casini
    • 1
  • Guido Mastrobuoni
    • 2
  • Mattia Terenghi
    • 3
  • Chiara Gabbiani
    • 1
  • Enrico Monzani
    • 3
  • Gloriano Moneti
    • 2
  • Luigi Casella
    • 3
  • Luigi Messori
    • 1
    Email author
  1. 1.Department of ChemistryUniversity of FlorenceSesto FiorentinoItaly
  2. 2.Mass Spectrometry CenterUniversity of FlorenceSesto FiorentinoItaly
  3. 3.Department of ChemistryUniversity of PaviaPaviaItaly

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