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Primary sequence confirmation of the beta-amyloid peptide from hereditary cerebral haemorrhage with amyloidosis (Dutch type) by collisional activation of the doubly charged ion.

High-energy collisional activation of doubly charged peptide ions allows direct sequential analysis of peptides over 4 kDa, including leucine/isoleucine determinations. This technique was used to verify the sequence of an intact beta-amyloid peptide associated with hereditary cerebral haemorrhage with amyloidosis Dutch type (4.2 kDa), which resists both enzymatic digestion and Edman sequencing. Additionally, this approach shows promise for the primary sequence confirmation of a wide variety of large peptides by tandem mass spectrometry.