Electron Transfer Dissociation Mass Spectrometry of Peptides Containing Free Cysteine Using Group XII Metals as a Charge Carrier

Abstract

Electron transfer dissociation (ETD) has been used for peptide sequencing. Since ETD preferentially produces the c'/z(•) fragment pair, peptide sequencing is generally performed by interpretation of mass differences between series of consecutive c' and z(•) ions. However, the presence of free cysteine residues in a precursor promotes peptide bond cleavage, hindering interpretation of the ETD spectrum. In the present study, the divalent group XII metals, such as Zn(2+), Cd(2+) and Hg(2+), were used as charge carriers to produce metal-peptide complexes. The thiol group is deprotonated by complexation with the group XII metal. The formation of b and y' ions was successfully suppressed by using the zinc-peptide complex as a precursor, indicating Zn(2+)-aided ETD to be a useful method for sequencing of cysteine-containing peptides. By contrast, ETD of Cd(2+)- and Hg(2+)-peptide complexes mainly led to SH2 loss and radical cation formation, respectively. These processes were mediated by recombination energy between the metal cation and an electron. The presence of monovalent cadmium and neutral mercury in ETD products was confirmed by MS(3) analysis with collision-induced dissociation.

The Effects of Trivalent Lanthanide Cationization on the Electron Transfer Dissociation of Acidic Fibrinopeptide B and its Analogs

“…For several acidic peptides, Asakawa and coworkers [52] demonstrated that metallated peptide ions with 2+ or 3+ charges produced by cationization with potassium or calcium ions underwent more sequence-informative ETD as compared to dissociation of the analogous protonated ions. In another study, Asakawa and Wada [53] complexed peptides containing cysteine residues with three divalent metal ions. The nature of the metal affected the production of c- and z-ions by ETD.…”

Difference of Electron Capture and Transfer Dissociation Mass Spectrometry on Ni2+-, Cu2+-, and Zn2+-Polyhistidine Complexes in the Absence of Remote Protons

“…In the case of a protonated precursor, metal-peptide complexes give a c'/z• fragment pair by ECD/ETD for most metal cations [13][14][15][16][17][18][19], suggesting that the fragmentation proceed via Utah-Washington model. In contrast, transition metal cations with a partially filled d orbital shell, such as Co 2+ , Ni 2+ , and Cu 2+ , are reduced by ECD/ETD [15,20].…”

Dissociation of trivalent metal ion (Al3+, Ga3+, In3+ and Rh3+)–peptide complexes under electron capture dissociation conditions

“…Among the various charge carriers, the metal ion has gained special interest because it achieves the most diverse chemistry by forming various complexes with peptides. The effect of metal ions as charge carriers for ECD fragmentation of peptides has been investigated by several groups . It has been demonstrated that metal ions could tune the ECD pathways of peptides.…”