On the Mechanism of Electron-Capture-Induced Dissociation of Peptide Dications from <sup>15</sup>N-Labeling and Crown-Ether Complexation

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Electron transfer and capture mass spectra of a series of doubly charged ions that were phosphorylated pentapeptides of a tryptic type (pS,A,A,A,R) showed conspicuous differences in dissociations of charge-reduced ions. Electron transfer from both gaseous cesium atoms at 100 keV kinetic energies and fluoranthene anion radicals in an ion trap resulted in the loss of a hydrogen atom, ammonia, and backbone cleavages forming complete series of sequence z ions. Elimination of phosphoric acid was negligible. In contrast, capture of lowenergy electrons by doubly charged ions in a Penning ion trap induced loss of a hydrogen atom followed by elimination of phosphoric acid as the dominant dissociation channel. Backbone dissociations of charge-reduced ions also occurred but were accompanied by extensive fragmentation of the primary products. z-Ions that were terminated with a deaminated phosphoserine radical competitively eliminated phosphoric acid and H 2 PO 4 radicals. A mechanism is proposed for this novel dissociation on the basis of a computational analysis of reaction pathways and transition states. Electronic structure theory calculations in combination with extensive molecular dynamics mapping of the potential energy surface provided structures for the precursor phosphopeptide dications. Electron attachment produces a multitude of low lying electronic states in charge-reduced ions that determine their reactivity in backbone dissociations and H-atom loss. The predominant loss of H atoms in ECD is explained by a distortion of the Rydberg orbital space by the strong dipolar field of the peptide dication framework. The dipolar field steers the incoming electron to preferentially attach to the positively charged arginine side chain to form guanidinium radicals and trigger their dissociations.

Section: Dissociations Of Z Ionsmentioning

confidence: 99%

Section: Electron Attachment Energeticsmentioning

confidence: 99%

Dipole-Guided Electron Capture Causes Abnormal Dissociations of Phosphorylated Pentapeptides

Moss

Chung

Wyer

et al. 2011

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“…Figure 2d (Figure 2e), which differs from that for a random distribution of eight exchangeable deuterium atoms in the ion (7:7:1). This indicates that the incomplete exchange of eight of ten exchangeable protons in (AR ϩ 2H) 2ϩ mainly affects the Gly ammonium group, which is presumed to be lost preferentially upon ECID [25][26][27]. The D label distribution in the z ions from (ARϪD 6 ϩ 2D) 2ϩ shows a 4:8:3 We also studied the CID spectra of (GR ϩ H) ϩ and (AR ϩ H) ϩ to elucidate dissociations of these ions when formed as intermediates by the facile loss of H from the corresponding charge-reduced precursors.…”

Section: Ecid Spectra Of (Grmentioning

confidence: 99%

“…Specific 15 N isotope labeling of the Gly, Ala, or Arg residues [27] would be necessary to establish which of these mechanisms operates in ECID. Multiple reaction pathways were also found by computations for the NOC ␣ bond dissociations in (GR ϩ 2H) ϩ· , e.g., TS5, TS7, and TS8, that started from different precursor ion conformers and proceeded via different charge-reduced intermediates.…”

mentioning

confidence: 99%

Inverse hydrogen migration in arginine-containing peptide ions upon electron transfer

Panja

Nielsen

Hvelplund

et al. 2008

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Collisional electron transfer from gaseous Cs atoms was studied for singly and doubly protonated peptides Gly-Arg (GR) and Ala-Arg (AR) at 50-and 100-keV kinetic energies. Singly protonated GR and AR were discharged to radicals that in part rearranged by migration of a C ␣ hydrogen atom onto the guanidine group. The C ␣ -radical isomers formed were detected as stable anions following transfer of a second electron. In addition to the stabilizing rearrangements, the radicals underwent side-chain and backbone dissociations. The latter formed z fragments that were detected as the corresponding anions. Analysis of the (GR ϩ H) · radical potential energy surface using electronic structure theory in combination with Rice-Ramsperger-Kassel-Marcus calculations of rate constants indicated that the arginine C ␣ hydrogen atom was likely to be transferred to the arginine side-chain on the experimental timescale of Յ200 ns. Transfer of the Gly C ␣ OH was calculated to have a higher transitionstate energy and was not kinetically competitive. Collisional electron transfer to doubly protonated GR and AR resulted in complete dissociation of (GR ϩ 2H) ϩ· and (AR ϩ 2H) ϩ· ions by loss of H, ammonia, and NOC ␣ bond cleavage. Electronic structure theory analysis of (GR ϩ 2H) ϩ· indicated the presence of multiple conformers and electronic states that differed in reactivity and steered the dissociations to distinct channels. Electron attachment to (GR ϩ 2H) 2ϩ resulted in the formation of closely spaced electronic states of (GR ϩ 2H) ϩ· in which the electron density was delocalized over the guanidinium, ammonium, amide, and carboxyl groups. The different behavior of (GR ϩ H) · and (GR ϩ 2H) ϩ· is explained by the different timescales for dissociation and different internal energies acquired upon electron transfer. A rginine frequently occurs as a C-terminal residue in tryptic peptides used in bottom-up proteomics. Because of the high basicity of the guanidine group in the side chain, arginine residues at C-termini are invariably protonated in peptide ions produced by electrospray ionization. The ability of arginine to sequester a proton in the gas-phase peptide ion has a major effect on charge-driven ion dissociations induced by collisional activation [1].Less is known about the effects that Arg residues have on dissociations of charge-reduced peptide ions produced by electron capture or transfer [2]. For example, protonated Arg residues at C-termini have been reported to undergo preferential reduction upon electron capture and the dissociations mainly formed ion fragments that carried the remaining charge on the N-terminal Arg residue [3]. Recently, we have studied one-electron reduction of protonated arginine and arginine amide as model systems for related electron capture (ECD) [4] and electron-transfer dissociations (ETD)[5] of arginine-terminated peptides. Reduction of protonated functional groups in gas-phase peptide ions produces transient radical intermediates that have been considered to donate hydrogen atoms to amide carbo...

“…Second, ETD fragment ions by loss of ammonia from peptides of the Lys-C-terminated (AAXAK) series were studied. These correspond to [ • AAXAK + ], or [z 5 + H] +• , ions according to previous studies of ion structure that established that the ammonia molecule selectively originates from the peptide N-terminus [33,34]. Analogous fragment ions by ETD loss of ammonia from the Arg-C-terminated (AAXAR) series were not considered because they are likely to be mixtures of isomers formed by ammonia elimination from the N-terminus and the Arg side chain [19,34].…”

Section: Introductionmentioning

confidence: 99%

Near-UV Photodissociation of Tryptic Peptide Cation Radicals. Scope and Effects of Amino Acid Residues and Radical Sites

Nguyen

Tureček

2017

, where X = A, C, D, E, F, G, H, K, L, M, N, P, Y, and W, were generated by electron transfer dissociation of peptide dications and investigated by MS 3 -nearultraviolet photodissociation (UVPD) at 355 nm. Laser-pulse dependence measurements indicated that the ion populations were homogeneous for most X residues except phenylalanine. UVPD resulted in dissociations of backbone CO─NH bonds that were accompanied by hydrogen atom transfer, producing fragment ions of the [y n ] + type. Compared with collision-induced dissociation, UVPD yielded less sidechain dissociations even for residues that are sensitive to radical-induced side-chain bond cleavages. The backbone dissociations are triggered by transitions to second (B) excited electronic states in the peptide ion R-CH • -CONH-chromophores that are resonant with the 355-nm photon energy. Electron promotion increases the polarity of the B excited states, R-CH + -C • (O -)NH-, and steers the reaction to proceed by transfer of protons from proximate acidic C α and amide nitrogen positions.