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Issue 5, 2009
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Reactivity of an antimetastatic organometallicruthenium compound with metallothionein-2: relevance to the mechanism of action

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Abstract

The reaction of metallothionein-2 (MT-2) with the organometallic antitumour compound [Ru(η6-p-cymene)Cl2(pta)], RAPTA-C, was investigated using ESI MS and ICP AES. The studies were performed in comparison to cisplatin and significant differences in the binding of the two complexes were observed. RAPTA-C forms monoadducts with MT-2, at variance with cisplatin, that has been observed to form up to four adducts. These data, combined with ICP AES analysis, show that binding of both RAPTA-C and cisplatin to MT-2 requires the displacement of an equivalent amount of zinc, suggesting that Cys residues are the target binding sites for the two metallodrugs. The competitive binding of RAPTA-C and cisplatin towards a mixture of ubiquitin (Ub) and MT-2 was also studied, showing that MT-2 can abstract RAPTA-C from Ub more efficiently than it can abstract cisplatin. The mechanistic implications of these results are discussed.

Graphical abstract: Reactivity of an antimetastatic organometallicruthenium compound with metallothionein-2: relevance to the mechanism of action

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Publication details

The article was received on 08 May 2009, accepted on 22 Jul 2009 and first published on 11 Aug 2009


Article type: Paper
DOI: 10.1039/B909185H
Metallomics, 2009,1, 434-441

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    Reactivity of an antimetastatic organometallicruthenium compound with metallothionein-2: relevance to the mechanism of action

    A. Casini, A. Karotki, C. Gabbiani, F. Rugi, M. Vašák, L. Messori and P. J. Dyson, Metallomics, 2009, 1, 434
    DOI: 10.1039/B909185H

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