title: Fast-atom bombardment tandem mass spectrometry of cyclic nucleotide analogues used as site-selective activators of cyclic nucleotide-dependent protein kinases.
abstract: The mass spectrometric behaviour of six cyclic nucleotide analogues which activate cyclic AMP-dependent protein kinase was studied by positive-ion fast-atom bombardment (FAB) and collision-induced dissociation (CID) mass-analysed ion kinetic energy (MIKE) spectrometry. The compounds studied were 1,N6-ethenoadenosine-3',5'-cyclic monophosphate, (epsilon-cyclic AMP) and 2'-aza-1,N6-ethenoadenosine-3',5'-cyclic monophosphate, which each activate both isoforms of cyclic AMP-dependent protein kinase and have similar affinity for both the 'fast' and the 'slow' regulatory site of each isoform, N6-phenyl-cyclic AMP, which is selective for the 'fast' regulatory site of each isoform, and 6-chloropurine riboside-3',5'-cyclic monophosphate, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'-cyclic monophosphate and 8-(4-chlorophenylthio)-adenosine-3',5'-cyclic monophosphate, which are each selective for the 'slow' regulatory site and preferentially activate isoform II. The FAB- and CID/MIKE spectra of the analogues are discussed in relation to their use in studies of the regulation of protein kinase activity by quantitative FAB mass spectrometry.
authors.affiliation: Biochemistry Group, School of Biological Sciences, University of Wales Swansea, Singleton Park, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Walton
authors.forename: M A
authors.initials: MA
authors.lastname: Bayliss
authors.forename: M L
authors.initials: ML
authors.lastname: Pereira
authors.forename: D E
authors.initials: DE
authors.lastname: Games
authors.forename: H G
authors.initials: HG
authors.lastname: Genieser
authors.forename: A G
authors.initials: AG
authors.lastname: Brenton
authors.forename: F M
authors.initials: FM
authors.lastname: Harris
authors.forename: R P
authors.initials: RP
authors.lastname: Newton
mesh_terms: D000242:Cyclic AMP / Q000031:analogs & derivatives*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D011487:Protein Conformation; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases