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

Abstract

Abstract. Electron capture dissociation (ECD) and electron transfer dissociation (ETD) in metal-peptide complexes are dependent on the metal cation in the complex. The divalent transition metals Ni 2+ , Cu 2+ , and Zn 2+ were used as charge carriers to produce metal-polyhistidine complexes in the absence of remote protons, since these metal cations strongly bind to neutral histidine residues in peptides. In the case of the ECD and ETD of Cu 2+ -polyhistidine complexes, the metal cation in the complex was reduced and the recombination energy was redistributed throughout the peptide to lead a zwitterionic peptide form having a protonated histidine residue and a deprotonated amide nitrogen. The zwitterion then underwent peptide bond cleavage, producing a and b fragment ions. In contrast, ECD and ETD induced different fragmentation processes in Zn 2+ -polyhistidine complexes. Although the N-C α bond in the Zn 2+ -polyhistidine complex was cleaved by ETD, ECD of Zn 2+ -polyhistidine induced peptide bond cleavage accompanied with hydrogen atom release. The different fragmentation modes by ECD and ETD originated from the different electronic states of the charge-reduced complexes resulting from these processes. The details of the fragmentation processes were investigated by density functional theory.

Influence of the metals and ligands in dinuclear complexes on phosphopeptide sequencing by electron-transfer dissociation tandem mass spectrometry

“…Because the binding energy between (Cu2L1) 3+ and T18p was decreased by reduction of Cu 2+ in the complex, (CuL1) + and [T18p + Cu] + would be formed by ETD-MS/MS. This result is good agreement with previously reported ETD-MS/MS of Cu 2+ -peptide complex30 and the presence of Cu 2+ in the precursor ion suppress the N-Cα bond cleavage by ETD-MS/MS.Regarding the Figure4d, ETD of [Ga2L2 + (T18p -2H)] 3+ selectively induced C6H6N• losses, leading to the [Ga2L2 + (T18p -2H -C6H6N)] 2+ and [Ga2L2 + (T18p -2H -2C6H6N)] + . The C6H6N• loss was induced the electron association to the pyridine ring in the complex, and the N-Cα bond cleavage is completely suppressed by the presence of (Ga2L2) 5+ in the precursor.…”

“…However, the yield of metal-peptide complex is usually low when the free metal cation was used. [21][22]30 To increase the yield of metal-phosphopeptide complex, we have recently used a dinuclear zinc complex, (Zn2L1) 3+ (L1 = alkoxide form of 1,3-bis[bis(pyridin-2-ylmethyl)amino]propan-2-ol), also known as the phosphate capture molecule "phos-tag", [32][33][34] as an ionizing reagent. 16 The molecular structure of (Zn2L1) 3+ is shown in Scheme 1a.…”

“…[21][22]29 In contrast, transition metal cations with a partially filled d orbital shell, such as Co 2+ , Ni 2+ , and Cu 2+ , are reduced by ETD and the fragmentation is mainly induced by the substantial excitation attributable to the reduction energy of the metal cation in the complex. 30 Although Cd 2+ and Hg 2+ are closed shelled metal cation, Cd 2+ -and Hg 2+ -peptide complexes undergoes metal cation reduction by ETD, probably due to complex electron energy level of Cd 2+ and Hg 2+ . 22,31 The results suggest that the period 5, 6 and 7 metal cations were susceptible to undergo the reduction by ETD.…”

Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein

“…This indicates that in the case of this His-rich peptide, complexation with Zn 2+ had a considerable negative impact on overall fragmentation efficiency. In the light of literature findings showing that positively charged, non-redox-active ions support or enhance fragmentation 81 – 86 , we suggest that this inefficient cleavage for the Zn 2+ complex has structural origins ( vide infra ).…”

Replacing H+by Na+or K+in phosphopeptide anions and cations prevents electron capture dissociation

“… 115 Further, both ECD and ETD of 2+ ions of histidine peptides that lacked both amino groups and acidic sites (acetylation of the N-terminal amine and amidation of the C-terminal carboxylate), with Zn 2+ (∼8.6 eV), Ni 2+ (∼10.5 eV), or Cu 2+ (∼12.6 eV) attached, produced only a and b but no c , z ˙ or c ˙, z fragments. 116 In an ETD study of 15 different peptides, Vachet and Dong observed c and z ˙ fragments with Cu 2+ instead of Cu + attached, consistent with electron transfer to protonated sites instead of Cu 2+ . Moreover, they found a positive correlation between the number of residues that strongly bind Cu 2+ ( i.e.…”