Development of new methods for detailed analysis of peptides and proteins by mass spectrometry – University of Copenhagen

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Department of Pharmacy > Research > Section of Analytical Biosciences > Protein Analysis > Development of new met...

Development of new methods for detailed analysis of peptides and proteins by mass spectrometry

We are continually working to develop novel MS methods capable of characterizing the structural properties of proteins of therapeutic interest in greater details and with a higher throughput. New developments involve combined chromatography - mass spectrometry workflows capable of:

  • Rapid and efficient reduction of disulfide-bonds of proteins of therapeutic interest (Figure 1)
  • Measuring HDX of individual residues in proteins at higher resolution (Figure 2)
  • Rapidly survey the structural properties of biopharmaceuticals by ultrafast gas-phase hydrogen/deuterium exchange in the gas-phase (gas-phase HDX-MS), (Figure 3).

Figure 1. Rapid and efficient online reduction of disulfide-bonds by electrochemical reduction to improve information on therapeutic protein conformation and binding interactions from HDX-MS experiments. (Trabjerg et al., Anal. Chem 2015)

Figure 2. High-resolution HDX-MS experiments: integrating electron transfer dissociation MS/MS into the HDX-MS workflow (Rand et al. Acc. Chem. Res. 2014).

Figure 3. Ultrafast gas-phase HDX-MS inside the mass spectrometer for a rapid survey of peptide and protein structure (Mistarz et al. Anal. Chem. 2014).