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

Analysis of large peptides can be used to discover or to monitor biomarkers for various diseases. For example, the levels of such peptides can determine the effectiveness of an experimental drug or the progress of a disease. Many mass spectrometric methods for monitoring these peptides use MALDI-ToF instruments because of their high molecular weights, although such instruments typically lack MS/MS or MSn capabilities. Here, the m/z range of a MALDI-LIT instrument was extended to m/z 5500 for the MS or MSn analysis of large peptides. Instrument performance was examined using amyloid β 1−40 and 1−42 (avg. MW 4330.8 and 4515.0, respectively), large peptides that comprise the bulk of neuritic plaques and are potential biomarkers for Alzheimer's Disease. The amyloid β 1−40 was detected in the full-scan mass spectrum with sufficient resolution to distinguish and match the expected isotopic pattern. The MS/MS product ion spectra of both peptides matched the expected fragmentation patterns; up to MS4 experiments were performed to verify the identity of the peptides. These experiments clearly demonstrate the advantages of this approach, including MSn experiments for structural elucidation and simplified spectra due to singly charged parent ions, for large peptides.