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 neurodegenerativ e disorders. In order to evaluate mass spectrometric methods for the charac terization of intermolecular beta-sheet structures the hydrogen/deuterium e xchange 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 doma in and N- and C-terminal nonstructured octapeptide sequences, was measured by electrospray ionization mass spectrometry (ESI-MS) and matrix-assisted l aser desorption/ionization mass spectrometry (MALDI-MS). The kinetic analys is of the hydrogen/deuterium exchange (HX) shows that intermolecular beta-s heet structures contain slowly exchanging protons (k less than or equal to 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 kinet ics and the beta-sheet domains determined by ESI- and MALDI-MS were found t o correlate with the length and stability of the beta-structure domain of t he (VT)(n)-peptides. Copyright (C) 2000 John Wiley & Sons, Ltd.