Variable fragmentation and ionization of amyloid-beta epimers and isomers

While the existence of D-amino acids in peptides and proteins has recently been accepted in higher forms of life, their roles and importance are yet to be understood. The lack of analytical methods present for such epimeric and/or isomeric analyses often limits developments in the field. Studies have shown the elevated presence of epimeric and isomeric modifications to amyloid-beta (A beta) peptides extracted from Alzheimer's disease patients. These modifications most frequently occur through aspartic acid and serine residues. Because such peptides are indistinguishable by mass alone, selective liquid chromatography tandem mass spectrometry analysis is required to differentiate such peptides. Herein, we examine MS/MS of tryptic fragments of A beta peptides containing D-Asp, L-iso-Asp, D-iso-Asp, and/or D-Ser modifications. Peptide ionizability and fragmentation are explored through selected reaction monitoring, selected ion monitoring, and product ion scan. The results show the variability of ionization and fragmentation for many identical mass peptides and how these differences can affect the analysis of isomeric and epimeric peptides.

Automated summary

The existence of D-amino acids in peptides and proteins has been accepted in higher forms of life, but their roles and importance are not yet fully understood. The lack of analytical methods for such epimeric and isomeric analyses hampers the progress in this field. Studies have shown the presence of elevated levels of epimeric and isomeric modifications in Alzheimer's disease patients, particularly in amyloid-beta peptides. Selective liquid chromatography tandem mass spectrometry analysis is required to differentiate these peptides due to their indistinguishability by mass alone.