Transition metal ions: charge carriers that mediate the electron capture dissociation pathways of peptides.

Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Journal of the American Society for Mass Spectrometry (Impact Factor: 3.19). 09/2011; 22(12):2232-45. DOI: 10.1007/s13361-011-0246-1
Source: PubMed

ABSTRACT Electron capture dissociation (ECD) of model peptides adducted with first row divalent transition metal ions, including Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+), were investigated. Model peptides with general sequence of ZGGGXGGGZ were used as probes to unveil the ECD mechanism of metalated peptides, where X is either V or W; and Z is either R or N. Peptides metalated with different divalent transition metal ions were found to generate different ECD tandem mass spectra. ECD spectra of peptides metalated by Mn(2+) and Zn(2+) were similar to those generated by ECD of peptides adducted with alkaline earth metal ions. Series of c-/z-type fragment ions with and without metal ions were observed. ECD of Fe(2+), Co(2+), and Ni(2+) adducted peptides yielded abundant metalated a-/y-type fragment ions; whereas ECD of Cu(2+) adducted peptides generated predominantly metalated b-/y-type fragment ions. From the present experimental results, it was postulated that electronic configuration of metal ions is an important factor in determining the ECD behavior of the metalated peptides. Due presumably to the stability of the electronic configuration, metal ions with fully-filled (i.e., Zn(2+)) and half filled (i.e., Mn(2+)) d-orbitals might not capture the incoming electron. Dissociation of the metal ions adducted peptides would proceed through the usual ECD channel(s) via "hot-hydrogen" or "superbase" intermediates, to form series of c-/z(•)- fragments. For other transition metal ions studied, reduction of the metal ions might occur preferentially. The energy liberated by the metal ion reduction would provide enough internal energy to generate the "slow-heating" type of fragment ions, i.e., metalated a-/y- fragments and metalated b-/y- fragments.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The structures and collision-induced dissociation (CID) fragmentation patterns of the permethylated glycan Man5GlcNAc2 are investigated by a combination of hybrid ion mobility spectrometry (IMS), mass spectrometry (MS), and MS/MS techniques. IMS analysis of eight metal-adducted glycans ([Man5GlcNAc2 + M](2+), where M = Mn, Fe, Co, Ni, Cu, Mg, Ca, and Ba) shows distinct conformer patterns. These conformers appear to arise from individual metals binding at different sites on the glycan. Fragmentation studies suggest that these different binding sites influence the CID fragmentation patterns. This paper describes a series of separation, activation, and fragmentation studies that assess which fragments arise from each of the different gas-phase conformer states. Comparison of the glycan distributions formed under gentle ionization conditions with those obtained after activation of the gas-phase ions suggests that these conformer binding states also appear to exist in solution.
    Journal of the American Society for Mass Spectrometry 10/2014; 26(1). DOI:10.1007/s13361-014-1000-2 · 3.19 Impact Factor
  • [Show abstract] [Hide abstract]
    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 Journal of Physical Chemistry B 10/2014; 118(43). DOI:10.1021/jp502818u · 3.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The collisionally activated dissociation (CAD) and electron capture dissociation (ECD) of doubly charged tocopheryl polyethylene glycol succinate (TPGS) have been examined. Li(+), Na(+), K(+), Ag(+), and H(+) were selected in the study, and the competitive influence of each ion was investigated by fragmenting TPGS attached with two different cations, [M + X1 + X2](2+) (X1 and X2 refer to Li(+), Na(+), K(+), Ag(+), H(+)). For metallic adducts, CAD results show that the dissociation of ionic adducts from the precursor is most likely depending on the binding strength, where the affinity of each ion to the TPGS is in the order of Ag(+) ≈ Li(+) ˃ Na(+) ˃ K(+). Introducing more strongly bound adducts increases fragmentation. During ECD, however, the silver cation is lost most easily compared with the other alkali metal ions, but silver also shows a dominant role in producing fragmentations. Moreover, the charge carriers are lost in an order (Ag(+) ˃ Na(+) ˃ K(+) ≥ Li(+) where the loss of Ag is most easily) that appears to correlate with the standard reduction potential of the metallic ions (Ag(+) ˃ Na(+) ˃ K(+) ˃ Li(+)). The ECD results suggest that the reduction potential of the charge carrier could be an important factor influencing the fragmentation, where the ion with a high reduction potential is more effective in capturing electrons, but may also be lost easily before leading to any fragmentation. Finally, a proton has the weakest binding with the TPGS according to the CAD results, and its dissociation in ECD follows the order of the reduction potential (Ag(+) ˃ H(+) ˃ Na(+) ˃ K(+) > Li(+)).
    Journal of the American Society for Mass Spectrometry 10/2014; 26(1). DOI:10.1007/s13361-014-1009-6 · 3.19 Impact Factor

Full-text (2 Sources)

Available from
May 20, 2014