Charge effects for differentiation of oligodeoxynucleotide isomers containing 8-oxo-dG residues
Dissociation reactions of a series of multiply charged oligodeoxynucleotide (ODN) 12-mer anions were studied using an ion trap mass spectrometer. These mixed nucleobase 12-mers fragment first by loss of a neutral nucleobase (A, G, C, and/or 5-methyl-cytosine) followed by cleavage at 3′ C-O bond of the sugar from which the base is lost to produce the complementary sequence ions, i.e., [a – B] and w type of ions. No detectable loss of 8-oxo-guanine and/or thymine from these 12-mers is observed under gentle collision conditions in the ion trap. The primary loss of a nucleobase and the subsequent backbone cleavage to generate sequence ions strongly depend on the charge state of the parent molecular ion. For low charge states (2- and 3-), product ions due to the loss of a neutral guanine base and related sequence ions are dominant in the tandem mass spectra. However, preferential loss of a neutral adenine becomes the primary reaction channel from the 5- charge state of the molecular ion. Such charge state dependent fragmentation behavior was utilized to determine the site of 8-oxo-dG residue in a series of structural isomers. The position of 8-oxo-dG residue can be simply determined from the fragmentation pattern of 3- charge state, but not of 5- charge state. It is suggested that in addition to specific modification that affects the N-glycosidic bond strength, total charge content of an ODN is an important factor for determining the differential fragmentation behavior.
- 14.Muddiman, D. C.; Cheng, X.; Udseth, H. R.; Smith, R. D. Charge-State Reduction with Improved Signal Intensity of Oligonucleotides in Electrospray Ionization Mass Spectrometry. J. Am. Soc. Mass Spectrom. 1996, 7, 697–706.Google Scholar
- 17.Bialkowski, K.; Cysewski, P.; Olinski, R. Effect of 2′-deoxyguanosine Oxidation at C8 Position on N-glycosidic Bond Stability. Z. Naturforsch. C 1996, 51, 119–122.Google Scholar