Dasatinib, imatinib and staurosporine capture compounds - Complementary tools for the profiling of kinases by Capture Compound Mass Spectrometry (CCMS)

作者：Fischer Jenny J; Dalhoff Christian; Schrey Anna K; Baessler Olivia Y Graebner Nee; Michaelis Simon; Andrich Kathrin; Glinski Mirko; Kroll Friedrich; Sefkow Michael; Dreger Mathias^*; Koester Hubert

来源：Journal of Proteomics, 2011, 75(1): 160-168.

DOI：10.1016/j.jprot.2011.05.035

• Chemical proteomics
• Capture Compound
• Mass Spectrometry
• Kinases
• Dasatinib
• Imatinib
• Staurosporine

Capture Compound Mass Spectrometry (CCMS) is a platform technology for the functional isolation of subproteomes. Here we report the synthesis of two new kinase Capture Compounds (CCs) based on the tyrosine-kinase specific inhibitors dasatinib and imatinib and compare their interaction profiles to that of our previously reported staurosporine-CCs. CCs are tri-functional molecules: they comprise a sorting e.g. the small molecule or drug of interest) which interacts with target proteins, a photo-activatable reactivity function to covalently trap the interacting proteins, and a sorting function to isolate the CC-protein conjugates from complex biological samples for protein identification by liquid chromatography/mass spectrometry (LC-MS/MS). We present data of CCMS experiments from human HepG2 cells and compare the profiles of the kinases isolated with dasatinib, imatinib and staurosporine CC, respectively. Dasatinib and imatinib have a more selective kinase binding profile than staurosporine. Moreover, the new CCs allow isolation and identification of additional kinases, complementing the staurosporine CC. The family of kinase CCs will be a valuable tool for the proteomic profiling of this important protein class. Besides sets of expected kinases we identified additional specific interactors; these off-targets may be of relevance in the view of the pharmacological profile of dasatinib and imatinib.

• 出版日期2011-12-10