Hydrogen exchange studies on Alzheimer's amyloid‐β peptides by mass spectrometry using matrix‐assisted laser desorption/ionization and electrospray ionization

The conformation and aggregation behavior of synthetic Alzheimer's amyloid peptides (A β ) 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 A β peptides was carried out by collision‐induced dissociation, inlet fragmentation, and post‐source decay. In contrast to the C‐terminally truncated peptides A β (1‐40) and A β (1‐36) showing full hydrogen‐deuterium exchange, A β (1‐42) and the pyroglutamyl peptide Pyr 3 ‐A β (3‐42) produced more complex signal patterns resulting from the formation of β‐sheet‐structured oligomers having 18–20 strongly protected protons. Using mass spectrometric fragmentation the results show that the reduced isotope exchange of A β (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 A β 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. Copyright © 2002 John Wiley & Sons, Ltd.