Peculiar mechanistic and structural features of the carboplatin-cytochrome c system revealed by ESI-MS analysis

Gabbiani, Chiara, Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542, Mastrobuoni, Guido, Kirshenbaum, Noam, Moshel, Ofra, Pieraccini, Giuseppe, Moneti, Gloriano, Messori, Luigi and Gibson, Dan 2008. Peculiar mechanistic and structural features of the carboplatin-cytochrome c system revealed by ESI-MS analysis. Journal of Biological Inorganic Chemistry 13 (5) , pp. 755-764. 10.1007/s00775-008-0361-z

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Abstract

Carboplatin (CPT), today the most important platinum(II) anticancer drug, manifests an extreme kinetic inertness, in vitro, at physiological pH; the actual mechanisms for its activation inside cells are still poorly understood. We show here that horse heart cytochrome c reacts with CPT, leading to the formation of stable platinum/protein adducts. The two major CPT–cytochrome c species resulting from the aforementioned reaction were characterised by electrospray ionisation mass spectrometry (ESI-MS). Notably, both these adducts have the ability to react with guanosine 5′-monophosphate (5′-GMP), giving rise to the respective cytochrome c–CPT–5′-GMP ternary complexes. Additional ESI-MS measurements on enzymatically cleaved cytochrome c adducts suggest that protein platination probably occurs at Met65. The mechanistic implications of these findings are discussed.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Publisher:	Springer
Last Modified:	31 Oct 2022 08:58
URI:	https://orca.cardiff.ac.uk/id/eprint/79362

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