title: Dasatinib, imatinib and staurosporine capture compounds - Complementary tools for the profiling of kinases by Capture Compound Mass Spectrometry (CCMS).
abstract: 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 function (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.
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Fischer
authors.forename: Christian
authors.initials: C
authors.lastname: Dalhoff
authors.forename: Anna K
authors.initials: AK
authors.lastname: Schrey
authors.forename: Olivia Y
authors.initials: OY
authors.lastname: Graebner
authors.forename: Simon
authors.initials: S
authors.lastname: Michaelis
authors.forename: Kathrin
authors.initials: K
authors.lastname: Andrich
authors.forename: Mirko
authors.initials: M
authors.lastname: Glinski
authors.forename: Friedrich
authors.initials: F
authors.lastname: Kroll
authors.forename: Michael
authors.initials: M
authors.lastname: Sefkow
authors.forename: Mathias
authors.initials: M
authors.lastname: Dreger
authors.forename: Hubert
authors.initials: H
authors.lastname: Koester
mesh_terms: D001549:Benzamides; D002853:Chromatography, Liquid / Q000379:methods; D000069439:Dasatinib; D020869:Gene Expression Profiling / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013058:Mass Spectrometry / Q000379:methods; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D019311:Staurosporine / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011494:Protein Kinases; D019311:Staurosporine; D000069439:Dasatinib