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

The reaction of metallothionein-2 (MT-2) with the organometallic antitumour compound [Ru(eta(6)-p-cymene)Cl-2(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.

Published in:
Metallomics, 1, 434-441

 Record created 2010-11-30, last modified 2018-03-17

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