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
|
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: | 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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