Analysis of Large Peptides by MALDI Using a Linear Quadrupole Ion Trap with Mass Range Extension

摘要

Analysis of large peptides can be used to discover or tonmonitor biomarkers for various diseases. For example, thenlevels of such peptides can determine the effectiveness ofnan experimental drug or the progress of a disease. Manynmass spectrometric methods for monitoring these peptidesnuse MALDI-ToF instruments because of their high molecularnweights, although such instruments typically lack MSMS or MSn capabilities. Here, them/z range of a MALDILITninstrument was extended tom/z 5500 for the MS ornMSn analysis of large peptides. Instrument performancenwas examined using amyloid u0001 1-40 and 1-42 (avg.nMW 4330.8 and 4515.0, respectively), large peptidesnthat comprise the bulk of neuritic plaques and arenpotential biomarkers for Alzheimer’s Disease. The amyloidnu0001 1-40 was detected in the full-scan mass spectrumnwith sufficient resolution to distinguish and match thenexpected isotopic pattern. The MS/MS product ionnspectra of both peptides matched the expected fragmentationnpatterns; up to MS4 experiments were performednto verify the identity of the peptides. These experimentsnclearly demonstrate the advantages of this approach,nincluding MSn experiments for structural elucidation andnsimplified spectra due to singly charged parent ions, fornlarge peptides.