Fragmentation energetics of small peptides from multiple-collision activation and surface-induced dissociation in FT-ICR MS

Multiple-collision activation (MCA-CID) using the sustained off-resonance irradiation (SORI) method and surface-induced dissociation (SID) of protonated tri- and tetraalanine (AAA)H+ and (AAAA)H+ were investigated using a 7 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS). Energy-resolved fragmentation efficiency curves (FECs) obtained using both activation techniques were modeled using RRKM/QET formalism. Comparison of rates of formation of fragment ions originating from C- and N-terminal dissociation of protonated tetraalanine as a function of collision energy demonstrates that threshold energies for these dissociation channels are identical and that entropic factors are very similar. For tetraalanine modeling of both SID and MCA-CID experimental results provides reliable values for dissociation thresholds for the principal dissociation channels. However, this is not the case for protonated trialanine, where C-terminal. fragmentation is preferred entropically but has higher dissociation energy and a slower rate over the range of collision energies investigated. Dissociation thresholds for the formation of y ions extracted from MCA-CID data for trialanine were substantially higher than thresholds obtained from SID data. Because our modeling approach assumes instantaneous ion activation, this difference is attributed to the slow nature of MCA-CID that becomes apparent for competing reactions with a substantial difference between dissociation thresholds. In this case, fragmentation via a higher-energy channel competes with stepwise ion activation. Consequently, MCA-CID results in effective discrimination against higher activation energy fragmentation pathways. For the series di-, tri-, and tetraalanine the lowest energy dissociation channels have thermochemical thresholds of 2.11, 1.46 and 1.20 eV, respectively based on our SID results. This demonstrates that thermochemical stability decreases with increasing size of the peptide. (C) 2002 Elsevier Science B.V. All rights reserved.