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

Gabbiani, Chiara, Casini, Angela, 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: 04 Jun 2017 08:30
URI: http://orca.cf.ac.uk/id/eprint/79362

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Cited 35 times in Scopus. View in Scopus. Powered By Scopus® Data

Cited 28 times in Web of Science. View in Web of Science.

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