Electrospray ionization and tandem mass spectrometry of cysteinyl eicosanoids: leukotriene C4 and FOG7.
The cysteinyl leukotrienes, LTC4, LTD4 and LTE4, and the recently described cysteinyl eicosanoid, 5-oxo-7-glutathionyl-8,11,14-eicosatrienoic acid (FOG7) have been analyzed by tandem mass spectrometry. Both [M-H]- and [M+H]+ ions were produced by electrospray ionization and collision-induced dissociation of these molecular ion species were studied using both an ion trap and a triple quadrupole instrument. Product ion spectra obtained were characteristic of the structure of the cysteinyl leukotrienes and mechanisms of ion formation were investigated by using deuterium-labeled analogs. The product ion spectrum obtained following collision-induced dissociation of the [M-H]- anion from FOG7 was devoid of significant structural information and further studies of collision activation of the [M+H]+ spectrum were therefore examined. Positive ion MS3 spectra obtained in the ion trap from the gamma-glutamate cleavage products of FOG7 and its derivative (d7-FOG7) afforded an abundant ion not observed in spectra generated from the cysteinyl leukotrienes. Formation of this fragment ion likely occurred via a McLafferty-type rearrangement to afford cleavage of the C6-C7 bond adjacent to the sulfur atom and was valuable for the identification of the structure of FOG7 and defining the biosynthetic pathway as a 1,4-Michael addition of glutathione to 5-oxo-eicosatetraenoic acid (5-oxo-ETE).
Hevko
J M
JM
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
Murphy
R C
RC
D016718:Arachidonic Acid / Q000032:analysis* / Q000138:chemical synthesis; D002630:Chemotactic Factors / Q000032:analysis* / Q000138:chemical synthesis; D005978:Glutathione / Q000032:analysis* / Q000138:chemical synthesis; D017997:Leukotriene C4 / Q000032:analysis* / Q000138:chemical synthesis; D021241:Spectrometry, Mass, Electrospray Ionization
D002630:Chemotactic Factors; C414562:FOG7 chemotactic; D016718:Arachidonic Acid; D017997:Leukotriene C4; D005978:Glutathione