Fast-atom bombardment tandem mass spectrometry of cyclic nucleotide analogues used as site-selective activators of cyclic nucleotide-dependent protein kinases

✍ Scribed by Terence J. Walton; Mark A. Bayliss; M. Luisa Pereira; David E. Games; H.-G. Genieser; A. Gareth Brenton; Frank M. Harris; Russell P. Newton

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 167 KB
• Volume: 12
• Category: Article
• ISSN: 0951-4198
• DOI: 10.1002/(sici)1097-0231(19980430)12:8<449::aid-rcm174>3.0.co;2-v

✦ Synopsis

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,N 6 -ethenoadenosine-3',5'-cyclic monophosphate (-cyclic AMP) and 2'-aza-1,N 6 -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, N 6 -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-b-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.