title: Design, synthesis and characterization of "clickable" 4-anilinoquinazoline kinase inhibitors.
abstract: Immobilized kinase inhibitors have emerged as powerful reagents for the determination of kinase inhibitor selectivity and for the enrichment of protein targets from cellular lysates. Here, we report the design and synthesis of a set of "clickable" 4-anilinoquinazoline kinase inhibitors. We demonstrate that the attachment of a flexible tether that contains a bio-orthogonal azide functionality does not adversely affect the potency or selectivity of these inhibitors. Furthermore, we demonstrate the utility of these inhibitors through the generation of an affinity matrix for the enrichment of interacting proteins from cellular lysates.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: B Gayani K
authors.initials: BG
authors.lastname: Perera
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Maly
mesh_terms: D064127:Aurora Kinases; D001665:Binding Sites; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D019061:src-Family Kinases; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases