Mass spectrometric identification of 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid during oxidation of 8-oxoguanosine by peroxynitrite and KHSO5/CoCl2.
Several products were previously identified from the reaction of 8-oxodG with bolus additions of peroxynitrite. Those experiments involved very high instantaneous concentrations of peroxynitrite and raised the possibility that the product spectrum may have differed from what might occur in vivo where much lower--and steadier--peroxynitrite levels would be expected. We consequently examined this issue by treating 2',3',5'-tri-O-acetyl-8-oxoGuo with infused authentic peroxynitrite and 3-morpholinosydnonimine and have found that under these conditions an additional product, not found under bolus addition conditions, was observed. Using tandem mass spectrometry, isotope labeling, and synthesis of a structural analogue, this compound was identified as 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid (HICA). The mechanism of HICA formation is rationalized by water attack at C5 of a quininoid intermediate.
Niles
Jacquin C
JC
Biological Engineering Division and Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 56-738A, Cambridge, Massachusetts 02139, USA.
Wishnok
John S
JS
Tannenbaum
Steven R
SR
D002264:Carboxylic Acids / Q000737:chemistry*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D048289:Imidazolidines / Q000737:chemistry*; D009566:Nitrates / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
C499514:4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid; D002264:Carboxylic Acids; D048289:Imidazolidines; D009566:Nitrates; D016877:Oxidants; D006151:Guanosine; C039642:peroxynitric acid; C046215:8-hydroxyguanosine