Electron Capture Dissociation of Peptides Adducted with Transition Metal Ions

In order to improve the performance of the electron capture dissociation (BCD) mass spectrometry for structural analysis of peptides/proteins, BCD of peptides cationized with various transition metal ions was investigated. It was found that peptides adducted with different divalent transition metal ions generated different BCD tandem mass spectra. For Mn2+and Zn2+, the incoming low-energy electron would not favor being trapped by the metal ions and instead trigger the usual BCD dissociation channel(s) via "hot-hydrogen" or "superbase" intermediates to form a series of c-/z·- fragments. For other first row transition metal ions, including Fe2+, Co2+, Ni 2+and Cu2+, reduction of the metal ions occurs preferentially during the electron capture event and lead to the formation of usual "slow-heating" type of fragment ions, i.e. metalated a-/y-fragments & metalated b-/y- fragments.;To further compare the behavior of metal ions with the same electronic configuration, BCD of Group IIB metal ions adducted peptides were investigated. In contrast to the ECD behavior of Zn2+ adducted peptides, peptide radical cations (M+·) and fragment ions corresponding to losses of neutral side chain from M+· were observed in the ECD spectra of Hg2+ and Cd 2+ adducted peptides. The experimental observations appeared to depend on the balance of the ionization energy of peptide and the solvation modulated ionization energies of the metal atom. The reduction of divalent metal ions by the electron capture event could induce spontaneous electron transfer from the peptide moiety to the monovalent metal centre and generate hydrogen-deficient M+· species.;As an additional study, effect of tyrosine nitration on the BCD of protonated and metalated peptides was investigated. Some fragment ions that were inhibited in the ECD of protonated peptides were liberated in the ECD of metalated peptides. By theoretical calculation of the cation-pi and cation-nitro group coordination using the metal ions nitrated phenol complex as a model, it is found that the metal ions might favor coordinating with the nitro group of the nitrated tyrosine residue in the peptides.