Stability of an organometallic ruthenium-ubiquitin adduct in the presence of glutathione: Relevance to antitumour activity

Christian G. Hartinger, Angela Casini, Céline Duhot, Yury O. Tsybin, Luigi Messori, Paul J. Dyson

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The interactions of the ruthenium(II) complex Ru(η6-p-cymene)(pta)Cl2 (RAPTA-C), an effective anticancer and antimetastatic agent, with biological nucleophiles are important with respect to its mechanism of action, for example, the reaction with glutathione (GSH) potentially plays an important role in detoxification. RAPTA-C reacts rapidly with glutathione forming a series of adducts including Ru(η6-p-cymene)(pta)(GS), Ru(η6-p-cymene)(GS) and bis-GSH conjugates, which were characterised by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In addition, the ability of glutathione to cleave ruthenium-ubiquitin bonds was assayed and it was shown that GSH is capable of removing the Ru moiety from the protein, although no ternary adducts were identified.

Original languageEnglish
Pages (from-to)2136-2141
Number of pages6
JournalJournal of Inorganic Biochemistry
Volume102
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

Keywords

  • Anticancer drugs
  • Bioorganometallic chemistry
  • FT-ICR mass spectrometry
  • Glutathione
  • Ruthenium complex

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