Can relative cleavage frequencies in peptides provide additional sequence information?

The ambiguity of attributing N- vs. C-terminal origin to a fragment ion can pose a problem in mass spectrometric de novo peptide sequencing even when all inter-residue bonds are cleaved. This makes additional sequence information highly desirable, The question is investigated whether relative abundances of fragment ions in MS/MS are capable of providing this information. Statistical analysis of data on peptides 10-24 residues long reveled that the frequencies of N-C-alpha bond cleavage in electron capture dissociation (ECD) are less dependent upon the total number of basic sites, the charge states of the parent ions and the nature of the terminal group than the peptide bond fragmentation in collisionally activated dissociation (CAD). The consensus sequences in peptides of different lengths also showed similar fragmentation patterns, with the typical correlation factor of 0.7. The conclusion is that frequencies of ECD cleavages are promising as a source of additional sequence information provided that strong intra-molecular bonds are absent or broken prior to MS/MS analysis. (C) 2002 Elsevier Science B.V. All rights reserved.