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Fast‐atom bombardment mass spectrometric analysis of cyclic nucleotide and nucleotide triphosphate analogues used in studies of cyclic nucleotide‐related enzymes
Author(s) -
Langridge James I.,
Evans Andrea M.,
Walton Terence J.,
Harris Frank M.,
Brenton A. Gareth,
Newton Russell P.
Publication year - 1993
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1290070809
Subject(s) - chemistry , adenylyl cyclase , nucleotide , mass spectrum , fast atom bombardment , stereochemistry , cyclic nucleotide , mass spectrometry , enzyme , biochemistry , chromatography , gene
Two isomers of adenosine 3′,5′‐cyclic monophosphate, which show agonist and antagonist activity with cyclic AMP‐dependent protein kinase, were found to yield essentially identical positive‐ion fast‐atom bombardment (FAB) mass spectra, but S 1 and S 2 fragments of differing relative intensities in their collision‐induced dissociations, studied using mass‐analysed ion kinetic energy (CID/MIKE) spectra. Halogen‐substituted cyclic nucleotides, used in differentiating between protein kinase cyclic nucleotide binding sites, produced FAB mass spectra and CID/MIKE spectra with fragmentations generally analogous to those of the parent cyclic nucleotides; the bromo‐derivatives showed a greater propensity for dehalogenation than the chloro‐derivatives. The adenosine triphosphate analogues, adenylyl‐(β,γ‐methylene)‐diphosphate and adenylyl‐imidodiphosphate, alternative substrates for adenylyl cyclase, showed similar fragmentations with the methylene and imido groups blocking cleavage between the β and γ phosphate groups. The fragmentations observed are discussed in the context of the use of these compounds in the assay of protein kinase and adenylyl cyclase activity by quantitative mass spectrometry.