Computationally and Experimentally Derived General Rules for Fragmentation of Various Glycosyl Bonds in Sodium Adduct Oligosaccharides

Mechanisms of fragmentation of glycosyl bond linkages in various saccharides were investigated by using computational calculations to find general rules of fragmentation of sodiated oligosaccharides in mass spectrometry. The calculations revealed that alpha-Glc, alpha-Gal, beta-Man, alpha-Fuc, beta-GlcNAc, and beta-GalNAc linkages were cleaved more easily than beta-Glc, beta-Gal, and alpha-Man linkages because the transition states of the former were stabilized by the anomeric effect. The 1-6 linkage was more stable than the others, since saccharides with flexible 1-6 linkages were more stabilized in energy than the other linkages by the sodium cation. The sialyl linkage was the most labile of all the linkages investigated. Comparison of activation energies and binding affinities to the sodium cation revealed an increase in activation energy in proportion to the increment in binding affinity. The calculated stabilities of glycosylbonds were: alpha-Man(Man alpha 1-3Man, Man alpha 1-4Man, Man alpha 1-6Man) > beta-Gal (Gal beta 1-4Gal) > alpha-GalNAc (GalNAc alpha 1-4GalNAc) > beta-Man (Man beta 1-4GlcNAc) > alpha-Gal (Gal alpha 1-3Gal, Gal alpha 1-4Gal, Gal alpha 1-6Gal) > beta-Man(Man beta 1-4Man) > beta-GalNAc (GalNAc beta 1-4GalNAc) > alpha-Fuc (Fuc alpha 1-6GlcNAc) > alpha-Fuc (Fuc alpha 1-4GlcNAc) > beta-GlcNAc(GlcNAc beta 1-4GlcNAc) > alpha-Fuc (Fuc alpha 1-3GlcNAc) > alpha-NeuNAc (NeuNAc alpha 2-3Gal, NeuNAc alpha 2-6Gal; this result was close to the experimentally deduced trend. These theoretically and experimentally derived general rules for fragmentation should be useful for analyzing the experimentally obtained mass spectra of oligosaccharides.