Gas-Phase Fragmentation of Oligoproline Peptide Ions Lacking Easily Mobilizable Protons

Wieczorek, Robert; Kluczyk, Alicja; Stefanowicz, Piotr; Szewczuk, Zbigniew

doi:10.1007/s13361-013-0585-1

Cited by 30 publications

(27 citation statements)

References 39 publications

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“…The product ion spectra are used to match theoretical spectra generated from databases of ‘in silico’ digests of proteins and translated DNA for peptide sequencing. However, current search engines only take a few general fragment ions into account when matching the spectra to a database, while the influences of many other factors such as charge state, charge carrier, structure, and size of a peptide, as well as some sequence‐specific fragment ions on fragmentation patterns are limited considered . As a result, only a small percentage of the peptide fragmentation spectra are correctly matched to peptide sequences .…”

Section: Introductionmentioning

confidence: 99%

“…However, current search engines only take a few general fragment ions into account when matching the spectra to a database, while the influences of many other factors such as charge state, charge carrier, structure, and size of a peptide, as well as some sequence-specific fragment ions on fragmentation patterns are limited considered. [3][4][5][6][7][8][9][10] As a result, only a small percentage of the peptide fragmentation spectra are correctly matched to peptide sequences. [11] Such sequence-specific fragment ions can be used to increase the confidence of peptide identifications if their fragmentation rule is incorporated into peptide sequencing algorithms.…”

Section: Introductionmentioning

confidence: 99%

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Characteristic neutral loss of CH₃CHO from Thr-containing sodium-associated peptides

Wang

Wei

et al. 2015

J. Mass Spectrom.

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A characteristic neutral loss of 44 Da is observed in the MS/MS spectra of Thr-containing sodiated peptides. A combination of tandem mass spectrometry and quantum chemical calculations calculated at the B3LYP/6-311G (d, p) level of ab initio theory is used to elucidate this fragmentation pathway. The high resolution mass spectrometry data indicate this neutral loss is acetaldehyde lost from the side chain of Thr rather than CO2. The intensity of this neutral loss can be enhanced when Thr residue is far from the C-terminus and when the C-terminus is esterified as well. The mechanism of the acetaldehyde loss is proposed to adopt a McLafferty-type rearrangement reaction, which involves a proton transfer from the hydroxyl of Thr side chain to its C-terminal neighboring carbonyl oxygen inducing the cleavage of the Ca-Cβ bond. This mechanism is further supported by examining the fragmentation of a [GT(tBu)G + Na](+) peptide derivative and by comparing the product ion spectra of [M + Na-44](+) of [GTGA + Na](+) with [M + Na](+) of [GGGA + Na](+). A similar neutral loss of HCHO can also be detected in Ser-containing peptides. Our computational results reveal that the most stable [GTG + Na](+) ion is present as a tridentate charge-solvated structure and the dissociation leading to the 44 loss is dynamically and energetically favorable.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characteristic neutral loss of CH₃CHO from Thr-containing sodium-associated peptides

Wang

Wei

et al. 2015

J. Mass Spectrom.

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“…In our previous work, we developed an efficient and straightforward method of isotopic exchange of acidic α-C hydrogens in N,N,N-trialkylglycine residues in peptides and discussed the application of such deuterium-labeled quaternary ammonium salt analogs for quantitative analysis of peptides. [24] We also used peptides containing the α-C deuterated N,N,N-trialkylglycine residues to study the mechanisms of peptide fragmentation during CID experiments [25,26] as well as hydrogen scrambling in non-covalent complexes of peptides. [27] In this article, we present our research on sarcosine-containing peptides, concerning the base-catalyzed HDX of α-C protons in sarcosine residue and specific hydrogen scrambling in such peptides.…”

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confidence: 99%

The unusual hydrogen-deuterium exchange ofα-carbon protons inN-substituted glycine-containing peptides

et al. 2014

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Hydrogens connected to α-carbon (α-C) of amino acid residues are usually resistant to hydrogen-deuterium exchange (HDX) unless reaction conditions promote racemization. Although N-methylglycine (sarcosine) residue has been found in biologically active peptide such as cyclosporine, to the best of our knowledge, the HDX of α-C protons of this residue was not explored yet. Here, we presented a new and efficient methodology of α-C deuteration in sarcosine residues under basic aqueous conditions. The deuterons, introduced at α-C atom, do not undergo back-exchange in acidic aqueous solution. The electrospray ionization-MS and MS/MS experiments on proposed model peptides confirmed the HDX at α-C and revealed the unexpected hydrogen scrambling in sarcosine-containing peptides. Although the observed HDX of α-C protons is only successful in N-acylglycine when the amide possesses a certain degree of alkylation, it offers a new approach to the analysis of sarcosine-containing peptides such as cyclosporine.

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“…This study suggested that the presence of the acidic N-H a bond was crucial for the formation of peptide-y-ions. Recently, Szewczuk and coworkers carried out a series of studies on the fragmentation pathways in N-substituted oligopeptides, including oligoproline and oligosarcosine, with a quaternary ammonium (QA) group tagged at the N-terminus [56,57]. These peptides did not contain backbone N-H groups.…”

Section: Fragmentation Mechanism: Y-ion Formationmentioning

confidence: 99%

Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation

Ren¹,

Tian²,

Hossain³

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. Peptoids are peptide-mimicking oligomers consisting of N-alkylated glycine units. The fragmentation patterns for six singly and doubly protonated model peptoids were studied via collision-induced dissociation tandem mass spectrometry. The experiments were carried out on a triple quadrupole mass spectrometer with an electrospray ionization source. Both singly and doubly protonated peptoids were found to fragment mainly at the backbone amide bonds to produce peptoid B-type N-terminal fragment ions and Y-type C-terminal fragment ions. However, the relative abundances of B-versus Y-ions were significantly different. The singly protonated peptoids fragmented by producing highly abundant Y-ions and lesser abundant Bions. The Y-ion formation mechanism was studied through calculating the energetics of truncated peptoid fragment ions using density functional theory and by controlled experiments. The results indicated that Y-ions were likely formed by transferring a proton from the C-H bond of the N-terminal fragments to the secondary amine of the C-terminal fragments. This proton transfer is energetically favored, and is in accord with the observation of abundant Y-ions. The calculations also indicated that doubly protonated peptoids would fragment at an amide bond close to the N-terminus to yield a high abundance of low-mass B-ions and high-mass Y-ions. The results of this study provide further understanding of the mechanisms of peptoid fragmentation and, therefore, are a valuable guide for de novo sequencing of peptoid libraries synthesized via combinatorial chemistry.

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Gas-Phase Fragmentation of Oligoproline Peptide Ions Lacking Easily Mobilizable Protons

Cited by 30 publications

References 39 publications

Characteristic neutral loss of CH₃CHO from Thr-containing sodium-associated peptides

Characteristic neutral loss of CH₃CHO from Thr-containing sodium-associated peptides

The unusual hydrogen-deuterium exchange ofα-carbon protons inN-substituted glycine-containing peptides

Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation

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Gas-Phase Fragmentation of Oligoproline Peptide Ions Lacking Easily Mobilizable Protons

Cited by 30 publications

References 39 publications

Characteristic neutral loss of CH3CHO from Thr-containing sodium-associated peptides

Characteristic neutral loss of CH3CHO from Thr-containing sodium-associated peptides

The unusual hydrogen-deuterium exchange ofα-carbon protons inN-substituted glycine-containing peptides

Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation

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Characteristic neutral loss of CH₃CHO from Thr-containing sodium-associated peptides

Characteristic neutral loss of CH₃CHO from Thr-containing sodium-associated peptides