title: Characterization of intermolecular beta-sheet peptides by mass spectrometry and hydrogen isotope exchange.
abstract: 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.
authors.affiliation: Forschungsinstitut für Molekulare Pharmakologie, Alfred-Kowalke-Strasse 4, D-10315 Berlin, Germany. kraus@fmp-berlin.de
authors.forename: M
authors.initials: M
authors.lastname: Kraus
authors.forename: K
authors.initials: K
authors.lastname: Janek
authors.forename: M
authors.initials: M
authors.lastname: Bienert
authors.forename: E
authors.initials: E
authors.lastname: Krause
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D003903:Deuterium; D006859:Hydrogen / Q000737:chemistry; D007700:Kinetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis* / Q000138:chemical synthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010455:Peptides; D006859:Hydrogen; D003903:Deuterium