Mapping the protein-binding sites for novel iridium(III) anticancer complexes using electron capture dissociation

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.