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

Casini, Angela, 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: 04 Jun 2017 08:30
URI: http://orca.cf.ac.uk/id/eprint/79358

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