Mass spectrometry is great for proteins (and peptides), but what happens when the proteins have carbohydrate modifications, or even when there is no protein/peptide “handle”? And when the analytes of interest are present as deviously complex mixtures, branched and fragile as well? This is the land of the glycobiologist and these are some of the challenges that must be met, if structures are to be determined and interactions are to be probed. The evolving tools of mass spectrometry must be evaluated and adapted to these challenges in order to meet the needs of this important field. We are investigating the behavior of free glycoproteins, glycopeptides and free glycans (and glycolipids) under various dissociation methods, with particular present focus on ExD, the range of new electron-based techniques that includes electron capture, electron transfer and electron detachment. These may be used alone, or, in MSn experiments, in combination with more traditional dissociation methods, e.g., CID and IRMPD. Key strategies and results from ongoing ion trap, Orbitrap and FTMS adventures in this area will be discussed. Acknowledgements: NIH-NCRR P41 RR10888, S10 RR020946, S10 RR025082.
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