Dissociation of the peptide bond in protonated peptides

Polce, Michael J.; Da, Ren; Wesdemiotis, Chrys

doi:10.1002/1096-9888(200012)35:12<1391::aid-jms85>3.3.co;2-t

Cited by 11 publications

(13 citation statements)

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“…Nucleophilic attack of the nitrogen of the N-terminal amino group on the carbon center of the protonated amide bond leads to the "diketopiperazine" pathways [18,22], compiled for a general oligopeptide in Scheme 4). Formation of the cyclic peptide and cleavage of the amide bond take place in a concerted manner and yield primarily the complex of the protonated cyclic peptide and the C-terminal fragment (amino acid or truncated peptide).…”

Section: The "Diketopiperazine" Pathwaysmentioning

confidence: 99%

“…Formation of the cyclic peptide and cleavage of the amide bond take place in a concerted manner and yield primarily the complex of the protonated cyclic peptide and the C-terminal fragment (amino acid or truncated peptide). Since the proton affinities of cyclic peptides are much lower those of linear peptides, the extra proton transfers to the C-terminal fragment and the complex dissociates to form the y ion and the cyclic peptide as its neutral counterpart [22]. The size of the cyclic peptide depends on how far the cleaved amide bond locates from the N-terminus.…”

Section: The "Diketopiperazine" Pathwaysmentioning

confidence: 99%

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Towards understanding the tandem mass spectra of protonated oligopeptides. 1: Mechanism of amide bond cleavage

Paizs

Suhai

2004

J. Am. Soc. Mass Spectrom.

152

168

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The mechanism of the cleavage of protonated amide bonds of oligopeptides is discussed in detail exploring the major energetic, kinetic, and entropy factors that determine the accessibility of the b(x)-y(z) (Paizs, B.; Suhai, S. Rapid Commun. Mass Spectrom. 2002, 16, 375) and "diketopiperazine" (Cordero, M. M.; Houser, J. J.; Wesdemiotis, C. Anal. Chem. 1993, 65, 1594) pathways. General considerations indicate that under low-energy collision conditions the majority of the sequence ions of protonated oligopeptides are formed on the b(x)-y(z) pathways which are energetically, kinetically, and entropically accessible. This is due to the facts that (1).the corresponding reactive configurations (amide N protonated species) can easily be formed during ion excitation, (2). most of the protonated nitrogens are stabilized by nearby amide oxygens making the spatial arrangement of the two amide bonds (the protonated and its N-terminal neighbor) involved in oxazolone formation entropically favored. On the other hand, formation of y ions on the diketopiperazine pathways is either kinetically or energetically or entropically controlled. The energetic control is due to the significant ring strain of small cyclic peptides that are co-formed with y ions (truncated protonated peptides) similar in size to the original peptide. The entropy control precludes formation of y ions much smaller than the original peptide since the attacking N-terminal amino group can rarely get close to the protonated amide bond buried by amide oxygens. Modeling the b(x)-y(z) pathways of protonated pentaalanine leads for the first time to semi-quantitative understanding of the tandem mass spectra of a protonated oligopeptide. Both the amide nitrogen protonated structures (reactive configurations for the amide bond cleavage) and the corresponding b(x)-y(z) transition structures are energetically more favored if protonation occurs closer to the C-terminus, e.g., considering these points the Ala(4)-Ala(5) amide bond is more favored than Ala(3)-Ala(4), and Ala(3)-Ala(4) is more favored than Ala(2)-Ala(3). This fact explains the increasing ion abundances observed for the b(2)/y(3), b(3)/y(2), and b(4)/y(1) ion pairs in the metastable ion and low-energy collision induced mass spectra (Yalcin, T.; Csizmadia, I. G.; Peterson, M. B.; Harrison, A. G. J. Am. Soc. Mass Spectrom. 1996, 7, 233) of protonated pentaalanine. A linear free-energy relationship is used to approximate the ratio of the b(x) and y(z) ions on the particular b(x)-y(z) pathways. Applying the necessary proton affinities such considerations satisfactorily explain for example dominance of the b(4) ion over y(1) and the similar b(3) and y(2) ion intensities observed for the metastable ion and low-energy collision induced mass spectra.

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Section: The "Diketopiperazine" Pathwaysmentioning

confidence: 99%

Section: The "Diketopiperazine" Pathwaysmentioning

confidence: 99%

Towards understanding the tandem mass spectra of protonated oligopeptides. 1: Mechanism of amide bond cleavage

Paizs

Suhai

2004

J. Am. Soc. Mass Spectrom.

152

168

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“…During CID, the cleavage of peptide bonds is typically governed by the mobility of a proton added during ionization, as explained by the mobile proton model 25,26. During collision-induced dissociation, the proton affinities of the peptide’s side chains determine the most stable locations for the available protons27,28 and thus profoundly affect proton mobility and by inference the likelihood of fragmentation of a particular amide bond. Other effects have been described linking peptide sequence to dominant spectral ions: cleavages C-terminal to acidic residues dominate the spectra of peptides that have a localized proton, and cleavages N-terminal to proline dominate the spectra of those that have a mobile or partially mobile proton 29,30.…”

Section: Introductionmentioning

confidence: 99%

Correlation between y-Type Ions Observed in Ion Trap and Triple Quadrupole Mass Spectrometers

et al. 2009

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Multiple reaction monitoring mass spectrometry (MRM-MS) is a technique for high-sensitivity targeted analysis. In proteomics, MRM-MS can be used to monitor and quantify a peptide based on the production of expected fragment peaks from the selected peptide precursor ion. The choice of which fragment ions to monitor in order to achieve maximum sensitivity in MRM-MS can potentially be guided by existing MS/MS spectra. However, because the majority of discovery experiments are performed on ion trap platforms, there is concern in the field regarding the generalizability of these spectra to MRM-MS on a triple quadrupole instrument. In light of this concern, many operators perform an optimization step to determine the most intense fragments for a target peptide on a triple quadrupole mass spectrometer. We have addressed this issue by targeting, on a triple quadrupole, the top six y-ion peaks from ion trap-derived consensus library spectra for 258 doubly charged peptides from three different sample sets and quantifying the observed elution curves. This analysis revealed a strong correlation between the y-ion peak rank order and relative intensity across platforms. This suggests that y-type ions obtained from ion trap-based library spectra are well-suited for generating MRM-MS assays for triple quadrupoles and that optimization is not required for each target peptide. Table 1, a description of the contents of the ISB standard 18 protein mix; Supplemental Table 2, the tabulated AUC and peak intensity data for the full combined data set; Supplemental Figure 1, the results for the rank order permutation test for the three individual data sets; Supplemental Figure 2, the results from the relative intensity randomization test for the three individual data sets; Supplemental Figure 3, the results from an alternative relative intensity randomization test in which the triple quadrupole spectra were randomized by permuting the existing relative intensities for each spectrum; Supplemental Figure 4, the results from a second alternative relative intensity randomization test in which the triple quadrupole spectra were randomized by replacing each peak intensity with a random value from the data set; and Supplemental Analysis, the secondary rank order analysis performed on the 142 excluded peptides. This material is available free of charge via the Internet at

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“…Early experimental studies suggested that the C-terminus-containing y fragments are simple truncated peptides [6,27,28]. While the complementary, N-terminus-containing b species were originally thought to be acylium ions [29], it is now generally accepted they instead have a five-membered oxazolone ring structure [4,5].…”

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confidence: 99%

Spectroscopic evidence for an oxazolone structure of the b₂ fragment ion from protonated tri-alanine

Oomens

Young

Molesworth

et al. 2009

J. Am. Soc. Mass Spectrom.

117

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Infrared multiple photon dissociation (IRMPD) spectroscopy is used to identify the structure of the b(2)(+) ion generated from protonated tri-alanine by collision induced dissociation (CID). The IRMPD spectrum of b(2)(+) differs markedly from that of protonated cyclo-alanine-alanine, demonstrating that the product is not a diketopiperazine. Instead, comparison of the IRMPD spectrum of b(2)(+) to spectra predicted by density functional theory provides compelling evidence for an oxazolone structure protonated at the oxazolone N-atom.

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Dissociation of the peptide bond in protonated peptides

Cited by 11 publications

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Towards understanding the tandem mass spectra of protonated oligopeptides. 1: Mechanism of amide bond cleavage

Towards understanding the tandem mass spectra of protonated oligopeptides. 1: Mechanism of amide bond cleavage

Correlation between y-Type Ions Observed in Ion Trap and Triple Quadrupole Mass Spectrometers

Spectroscopic evidence for an oxazolone structure of the b₂ fragment ion from protonated tri-alanine

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Dissociation of the peptide bond in protonated peptides

Cited by 11 publications

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Towards understanding the tandem mass spectra of protonated oligopeptides. 1: Mechanism of amide bond cleavage

Towards understanding the tandem mass spectra of protonated oligopeptides. 1: Mechanism of amide bond cleavage

Correlation between y-Type Ions Observed in Ion Trap and Triple Quadrupole Mass Spectrometers

Spectroscopic evidence for an oxazolone structure of the b2 fragment ion from protonated tri-alanine

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Spectroscopic evidence for an oxazolone structure of the b₂ fragment ion from protonated tri-alanine