Research Interests

The intrinsic chemical complexity and often identical mass of the building blocks in oligosaccharides often complicates their direct structural assignment on basis of conventional tandem MS data. Here we use ion mobility-derived structural information as an additional dimension for the MS-based analysis of complex carbohydrates. Experiments are performed on a commercially available hybrid tandem-IM-MS instrument in which the ions of interest can be fragmented prior or after IM separation.


Ion Mobility Mass Spectrometry of Complex Carbohydrates

Gas Phase Spectroscopy of Peptides and Proteins

In the condensed phase IR spectroscopy is a well established tool to investigate the structure and dynamics of proteins and their assemblies. This is based on the fact that the position of the characteristic amide I and amide II vibrational bands provides a direct measure of the molecules underlying secondary structure. In the absence of solvent, IR spectra can also be measured using action spectroscopy techniques. The absence of reference values for species with defined conformation as well as the typical peak broadening observed for larger molecules, however, so far restricted the applicability of the method to small molecules. Here we are aiming to extend the effective size-range of the method to folded proteins and protein complexes using conditions which are specifically optimized for a retention of the molecules conformation in the gas phase. Tunable infra red radiation for these experiments is provided by the FHI free electron laser.

One of the major advantages of MS and IM-MS is its ability to measure one species in the presence of others. This feature is already widely utilized for the analysis of complex mixtures and has recently been shown to be also of exceptional use for structural biology. Instead of adopting one defined oligomerization state, some proteins exist as equilibrium of several distinctly sized species. These so-called polydisperse assemblies cannot be analyzed directly by conventional solution phase methods, which exclusively yield data that reflect the average of the entire ensemble. With MS on the other hand, a particular non-covalently associated multimer can be probed directly out of its heterogeneous in vitro environment, which makes it an ideal tool for structural investigations on polydisperse systems.

The probably most relevant example of polydisperse systems are amyloid forming proteins as occurring in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. These proteins undergo a spontaneous transition from a soluble, often partially folded form into an insoluble, beta-sheet rich amyloid fibril. The underlying assembly pathway is not fully understood to date, but there has been increasing evidence that oligomeric folding intermediates that occur during the transformation process are the toxic species in the above mentioned diseases. Their structure however, is far from being understood. Here, we aim to characterize pre-selected oligomers of polydisperse protein assemblies regarding their secondary and tertiary structural arrangement using a combination of MS, IM-MS and gas phase spectroscopy techniques.

Protein Folding, Misfolding and Aggregation

Hoffmann, W.; Hofmann, J.; Pagel, K.; Energy Resolved Ion Mobility Mass Spectrometry - a Concept to Improve the Separation of Isomeric Carbohydrates. J. Am. Soc. Mass Spectrom. 2014, 25, 471-479.



Microsolvation of Gas-Phase Peptides and Proteins



There is ongoing debate on the extent to which protein structure is retained after transfer into the gas phase. Here using ion mobility mass spectrometry, we investigate the impact of side-chain backbone interactions on the structure of gas-phase protein ions by non-covalent attachment of crown ethers (CE). Our recent results indicate that in the absence of solvent, secondary interactions between charged lysine side chains and backbone carbonyls can significantly influence the structure of a protein. Once the charged residues are capped with CEs, certain charge states of the protein are found to undergo a significant structural compaction.

Excel spreadsheet to estimate CCSs from traveling wave ion mobility mass spectrometry data. See file for further details and literature. Click here and choose save link as


Schubert, F.; Pagel, K.; Rossi, M.; Warnke, S.; Salwiczek, M.; Koksch, B.; von Helden, G.; Blum, V., Baldauf, C.; Scheffler, M.; The beta-Peptide Equivalent of the alpha-Helix - Evidence from Experiment and Theory. submitted.