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

Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542, Karotki, Andrei, Gabbiani, Chiara, Rugi, Francesco, Vasak, Milan, Messori, Luigi and Dyson, Paul J. 2009. Reactivity of an antimetastatic organometallicruthenium compound with metallothionein-2: relevance to the mechanism of action. Metallomics 1 (5) , pp. 434-441. 10.1039/B909185H

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Royal Society of Chemistry
ISSN: 1756-5901
Date of Acceptance: 22 July 2009
Last Modified: 31 Oct 2022 08:58
URI: https://orca.cardiff.ac.uk/id/eprint/79358

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