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Mapping the protein‐binding sites for novel iridium(III) anticancer complexes using electron capture dissociation
Author(s) -
Qi Yulin,
Liu Zhe,
Li Huilin,
Sadler Peter J.,
O'Connor Peter B.
Publication year - 2013
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.6643
Subject(s) - chemistry , iridium , electron capture dissociation , dissociation (chemistry) , combinatorial chemistry , computational chemistry , mass spectrometry , biochemistry , chromatography , catalysis , tandem mass spectrometry
RATIONALE Application of Fourier transform ion cyclotron (FT‐ICR) tandem mass spectrometry reveals the binding sites for novel cyclopentadienyl Ir III anticancer complexes on calmodulin. The conventional fragmentation methods, collisionally activated dissociation (CAD) and infrared multiphoton dissociation (IRMPD), failed to define the Ir modification, but these binding sites were located via electron capture dissociation (ECD). METHODS A combination of top‐down and bottom‐up methods was used to generate detailed information about the reaction of these compounds with a common signalling protein, calmodulin. RESULTS The research shows that such Ir‐based complexes preferentially bind to methionine sites in the protein, and interestingly, the very low efficiency of the Ir modification is different compared to reactions of Pt II complexes, which can lead to protein crosslinking. CONCLUSIONS This is the first report on reactions of novel Ir‐based anticancer complexes with proteins, which provides helpful information for studying the protein targets of this category of metallodrug and the transportation mechanisms which allow them to inhibit cancer cell growth. Copyright © 2013 John Wiley & Sons, Ltd.