Characterization of intermolecular beta-sheet peptides by mass spectrometry and hydrogen isotope exchange.

The self-assembly of beta-sheet peptide domains resulting in the formation of fibrillar aggregates (amyloids) is a feature of various neurodegenerative disorders. In order to evaluate mass spectrometric methods for the characterization of intermolecular beta-sheet structures the hydrogen/deuterium exchange behaviour of model peptides DPKGDPKG-(VT)(n)-GKGDPKPD-amide (n = 3,4,5,6,7,8), (VT)(n)-peptides, composed of a central beta-sheet-forming domain and N- and C-terminal nonstructured octapeptide sequences, was measured by electrospray ionization mass spectrometry (ESI-MS) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The kinetic analysis of the hydrogen/deuterium exchange (HX) shows that intermolecular beta-sheet structures contain slowly exchanging protons (k </=0.001 1/min). Localization of beta-sheet domains was achieved by monitoring the hydrogen exchange of peptide fragments generated via collision-induced dissociation (CID) or post source decay (PSD). The hydrogen exchange kinetics and the beta-sheet domains determined by ESI- and MALDI-MS were found to correlate with the length and stability of the beta-structure domain of the (VT)(n)-peptides. Copyright 2000 John Wiley & Sons, Ltd.