Versatile tool for the analysis of metal-protein interactions reveals the promiscuity of metallodrug-protein interactions

Ronald F.S. Lee, Laure Menin, Luc Patiny, Daniel Ortiz, Paul J. Dyson

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)


Metallodrug-protein interactions contribute to their therapeutic effect (even when DNA is the dominant target), side-effects and are implicit in drug resistance. Here, we provide mass spectrometric-based evidence to show that metallodrug interactions with proteins are considerably more complex than current literature would suggest. Using native-like incubation and electrospray conditions together with an automated tool we designed for exhaustive mass spectra matching, the promiscuity of binding of cisplatin to ubiquitin is revealed, with 14 different binding sites observed. There is a binding preference to negatively charged sites on the protein, consistent with the cationic nature of the cisplatin adduct following aquation. These results have implications in metallodrug development and beyond to the toxicological effects of metal ions more generally.

Original languageEnglish
Pages (from-to)11985-11989
Number of pages5
JournalAnalytical Chemistry
Issue number22
Publication statusPublished - 21 Nov 2017
Externally publishedYes

Cite this