title: Affinity purification of proteins binding to kinase inhibitors immobilized on self-assembling monolayers.
abstract: Kinase inhibitors represent a relatively new class of drugs that offer novel therapies targeting specific -malfunctioning kinase-mediated signaling pathways in oncology and potentially inflammation. As the ATP binding sites of the ∼500 human kinases are structurally conserved and because most current drugs target the ATP binding site, there is a need to profile all the kinases that a drug may bind and/or inhibit. We have developed a chemical proteomics method that affinity purifies kinases from cell or tissue lysates using kinase inhibitors immobilized on self-assembling monolayers. The method can be applied to assess the selectivity of a given kinase inhibitor and thus to guide its preclinical or clinical development.
authors.affiliation: Cellzome AG, Heidelberg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bantscheff
authors.forename: Scott
authors.initials: S
authors.lastname: Hobson
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuster
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D002846:Chromatography, Affinity; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000302:isolation & purification* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D040901:Proteomics / Q000379:methods*
chemical_list: D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D010770:Phosphotransferases