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Sweet and Salty: the Fragmentation and Differentiation of Group II Cation Adducted Sialylated Human Milk Oligosaccharides by Electron Transfer Dissociation, Ion Mobility and Supplemental Vibrational Activation
Structural elucidation of underivatized isomeric carbohydrates has continued to be a challenge for the field of mass spectrometry. Human milk oligosaccharides (HMOs) have functions that range from their roles as prebiotics to their importance in neonatal brain development. Differentiation of HMO isomers by tandem mass spectrometry (MS/MS) remains a challenge because structural diversity. Previous research has shown that electron transfer dissociation (ETD) of a doubly charged metal cation adducted oligosaccharide can be separated using ion mobility (IM) and then fragmented by subsequent vibrational activation (VA) to produce unique fragments and dissociation pathways. This work explores the use of electron transfer–ion mobility–vibrational activation (ET-IM-VA) and targeted MSn experiments via sustained off-resonance irradiation-collision induced dissociation (SORI-CID) to study dissociation pathways of group II metal adducted sialyllacto-N-tetraose (LST) isomers. This dissertation describes the in-depth study of how energy resolved, electron transfer, ion mobility, and subsequent vibration activation methods can be used to investigate the fragmentation of LST isomers and explore the effects of group II metal cation adduction. ET-IM-VA was used to generate unique fragmentation pathways for each of the LST isomers as their group II metal adducts. Differences in relative fragment ion abundance was found to differentiate key structural features, such different linkages. Ion mobility experiments explored how charge state and group II metal adduction affected LST isomer arrival time distributions. The charge reduced LST and group II metal adducted species from the ion/ion reaction with nitrosobenzene radical anion were evaluated and found to be primarily proton transfer products instead of electron transfer products. Understanding fragmentation of native oligosaccharides remains underexplored, but with these studies, we have shown that a multidimensional approach can be utilized to differentiate model acidic oligosaccharide structures. The methods describe in this dissertation provide ways in which isomeric sialylated human milk oligosaccharides can be differentiated, which would benefit future studies of infant health and development.
Analytical chemistry|Neurosciences|Acoustics|Developmental biology|Obstetrics|Nutrition
Taylor, Anna J, "Sweet and Salty: the Fragmentation and Differentiation of Group II Cation Adducted Sialylated Human Milk Oligosaccharides by Electron Transfer Dissociation, Ion Mobility and Supplemental Vibrational Activation" (2020). ETD collection for University of Nebraska - Lincoln. AAI28258898.