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

Hartinger, Christian G., Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542, Duhot, Celine, Tsybin, Yury O., Messori, Luigi and Dyson, Paul J. 2008. Stability of an organometallic ruthenium-ubiquitin adduct in the presence of glutathione: relevance to antitumour activity. Journal of Inorganic Biochemistry 102 (12) , pp. 2136-2141. 10.1016/j.jinorgbio.2008.08.002

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Elsevier
Date of Acceptance:	13 August 2008
Last Modified:	31 Oct 2022 08:58
URI:	https://orca.cardiff.ac.uk/id/eprint/79359

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