Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
Rapid Commun Mass Spectrom. 2013 Sep 15;27(17):2028-32. doi: 10.1002/rcm.6643.
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).
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.
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.
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.
傅里叶变换离子回旋共振（FT-ICR）串联质谱法的应用揭示了新型环戊二烯基 Ir（III）抗癌配合物与钙调蛋白的结合位点。传统的碎片化方法，碰撞激活解离（CAD）和红外多光子解离（IRMPD），无法确定 Ir 的修饰，但这些结合位点是通过电子俘获解离（ECD）定位的。
采用自上而下和自下而上的方法相结合，生成这些化合物与常见信号蛋白钙调蛋白反应的详细信息。
研究表明，这种基于 Ir 的配合物优先与蛋白质中的蛋氨酸位点结合，有趣的是，与 Pt（II）配合物的反应相比，Ir 修饰的效率非常低，Pt（II）配合物可以导致蛋白质交联。
这是首例关于新型基于 Ir 的抗癌配合物与蛋白质反应的报道，为研究该类金属药物的蛋白质靶标以及允许它们抑制癌细胞生长的运输机制提供了有价值的信息。
