Influence of Metal–Peptide Complexation on Fragmentation and Inter-Fragment Hydrogen Migration in Electron Transfer Dissociation

Abstract

The use of metal salts in electrospray ionization (ESI) of peptides increases the charge state of peptide ions, facilitating electron transfer dissociation (ETD) in tandem mass spectrometry. In the present study, K(+) and Ca(2+) were used as charge carriers to form multiply-charged metal-peptide complexes. ETD of the potassium- or calcium-peptide complex was initiated by transfer of an electron to a proton remote from the metal cation, and a c'-z• fragment complex, in which the c' and z• fragments were linked together via a metal cation coordinating with several amino acid residues, was formed. The presence of a metal cation in the precursor for ETD increased the lifetime of the c'-z• fragment complex, eventually generating c• and z' fragments through inter-fragment hydrogen migration. The degree of hydrogen migration was dependent on the location of the metal cation in the metal-peptide complex, but was not reconciled with conformation of the precursor ion obtained by molecular mechanics simulation. In contrast, the location of the metal cation in the intermediate suggested by the ETD spectrum was in agreement with the conformation of "proton-removed" precursors, indicating that the charge reduction of precursor ions by ETD induces conformational rearrangement during the fragmentation process.

Effects of acidic peptide size and sequence on trivalent praseodymium adduction and electron transfer dissociation mass spectrometry

“…Sequence information from the resulting metallated peptide cations has been obtained in studies employing ECD [57][58][59][60][61][62][63][64][65][66][67][68] and ETD. [69][70][71][72] Flick and Williams [68] demonstrated the ability of trivalent lanthanide metal ions to produce multiply positively charged ions with peptides. During a recent ETD study [72] involving the addition of trivalent lanthanide metal cations to acidic peptides, we also noted that multiply charged metallated ions form by ESI even in the absence of a highly basic arginine amino acid residue (gas-phase basicity of arginine = 1006.6 kJ/mol [73] ).…”

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

“…Dong and Vachet [51] performed ETD on small copper-cationized peptides and observed c- and z-ions. 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.…”

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].…”