What Hinders Electron Transfer Dissociation (ETD) of DNA Cations?
Radical activation methods, such as electron transfer dissociation (ETD), produce structural information complementary to collision-induced dissociation. Herein, electron transfer dissociation of 3-fold protonated DNA hexamers was studied to gain insight into the fragmentation mechanism. The fragmentation patterns of a large set of DNA hexamers confirm cytosine as the primary target of electron transfer. The reported data reveal backbone cleavage by internal electron transfer from the nucleobase to the phosphate linker leading either to a•/w or d/z• ion pairs. This reaction pathway contrasts with previous findings on the dissociation processes after electron capture by DNA cations, suggesting multiple, parallel dissociation channels. However, all these channels merely result in partial fragmentation of the precursor ion because the charge-reduced DNA radical cations are quite stable. Two hypotheses are put forward to explain the low dissociation yield of DNA radical cations: it is either attributed to non-covalent interactions between complementary fragments or to the stabilization of the unpaired electron in stacked nucleobases. MS3 experiments suggest that the charge-reduced species is the intact oligonucleotide. Moreover, introducing abasic sites significantly increases the dissociation yield of DNA cations. Consequently, the stabilization of the unpaired electron by π–π-stacking provides an appropriate rationale for the high intensity of DNA radical cations after electron transfer.
KeywordsETD DNA radical cations Sugar-modified DNA Dissociation mechanism
The authors thank Professor Dr. Kathrin Breuker for the fruitful discussions of the present work.
- 19.Arcella, A., Dreyer, J., Ippoliti, E., Ivani, I., Portella, G., Gabelica, V., Carloni, P., Orozco, M.: Structure and dynamics of oligonucleotides in the gas phase. Angew. Chem. Int. Ed. 54, 467–471 (2015)Google Scholar
- 22.Böhringer, M., Roth, H.J., Hunziker, J., Göbel, M., Krishnan, R., Giger, A., Schweizer, B., Schreiber, J., Leumann, C., Eschenmoser, A.: Why pentose and not hexose nucleic-acids? Part II. Preparation of oligonucleotides containing 2',3'-dideoxy-b-D-glucopyranosyl building blocks. Helv. Chim. Acta. 75, 1416–1477 (1992)CrossRefGoogle Scholar
- 26.Glasner, H., Riml, C., Falschlunger, C., Micura, R., Breuker, K.: Characterization of intramolecular nucleobase–phosphate interactions by site-specific nucleobase methylation and collisionally activated dissociation. Proceedings of 65th ASMS Conference on Mass Spectrometry and Allied Topics, Indianapolis, IN, June 4–8 (2017)Google Scholar