title: Hydrogen exchange studies on Alzheimer's amyloid-beta peptides by mass spectrometry using matrix-assisted laser desorption/ionization and electrospray ionization.
abstract: The conformation and aggregation behavior of synthetic Alzheimer's amyloid peptides (Abeta) has been investigated using hydrogen-deuterium exchange measured by electrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry. Mass spectrometric fragmentation of deuterated Abeta peptides was carried out by collision-induced dissociation, inlet fragmentation, and post-source decay. In contrast to the C-terminally truncated peptides Abeta(1-40) and Abeta(1-36) showing full hydrogen-deuterium exchange, Abeta(1-42) and the pyroglutamyl peptide Pyr(3)-Abeta(3-42) produced more complex signal patterns resulting from the formation of beta-sheet-structured oligomers having 18-20 strongly protected protons. Using mass spectrometric fragmentation the results show that the reduced isotope exchange of Abeta(1-42) can be attributed to the central part of the chain comprising residues 8-23. This confirms involvement of the hydrophobic binding domain LVFFA in the course of Abeta aggregation and demonstrates that hydrogen-deuterium exchange in combination with mass spectrometry is well suited for structural analysis of monomeric and reversibly associated amyloid peptides using picomole quantities of material.
authors.affiliation: Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str 10, 13125 Berlin, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Kraus
authors.forename: Michael
authors.initials: M
authors.lastname: Bienert
authors.forename: Eberhard
authors.initials: E
authors.lastname: Krause
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003903:Deuterium / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D017434:Protein Structure, Tertiary; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides; D006859:Hydrogen; D003903:Deuterium