title: Synthesis and characterization of 5'-p-fluorosulfonylbenzoyl-2' (or 3')-(biotinyl)adenosine as an activity-based probe for protein kinases.
abstract: Most of the kinase inhibitors that are approved for therapeutic uses or that are undergoing clinical trials are directed toward the adenosine triphosphate (ATP) binding site of protein kinases. 5'-Fluorosulfonylbenzoyl 5'-adenosine (FSBA) is an activitybased probe (ABP) that covalently modifies a conserved lysine present in the nucleotide binding site of most kinases. Here the authors describe synthesis of FSBA derivatives, 2'-biotinyl-FSBA and 3'-biotinyl-FSBA as kinase ABPs, and delineate a Western blot method to screen and validate ATP competitive protein kinase inhibitors using biotinyl-FSBA as a nonselective activity-based probe for protein kinases.
authors.affiliation: High Throughput Chemistry, Stevenage, GlaxoSmithKline, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ratcliffe
authors.forename: Tracey
authors.initials: T
authors.lastname: Yi
authors.forename: Sanjay S
authors.initials: SS
authors.lastname: Khandekar
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001710:Biotin / Q000031:analogs & derivatives* / Q000032:analysis* / Q000138:chemical synthesis* / Q000737:chemistry; D015153:Blotting, Western; D002853:Chromatography, Liquid; D013058:Mass Spectrometry; D015335:Molecular Probes / Q000032:analysis* / Q000138:chemical synthesis*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D015335:Molecular Probes; D047428:Protein Kinase Inhibitors; D001710:Biotin; C010959:5'-(4-fluorosulfonylbenzoyl)adenosine; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D000241:Adenosine