On the Dynamics of Fragment Isomerization in Collision-Induced Dissociation of Peptides

Polfer, Nick C.; Bohrer, Brian C.; Plasencia, Manolo; Paizs, Béla; Clemmer, David E.

doi:10.1021/jp0763937

Cited by 84 publications

(112 citation statements)

References 38 publications

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“…Quantum chemical calculations indicated that the cyclic form is energetically more favored than the linear structures. Ion mobility experiments [22,31] confirmed that a ions have multiple structures. A recent CID and theoretical study [32] from our laboratories indicated that the CID spectra of a 5 fragments of YAGFL-NH 2 can reasonably be understood by assuming an interplay of b-type scrambling [20] of the corresponding b parent population and a ¡ a* type rearrangements [30].…”

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confidence: 87%

Structure and reactivity of a_n and a*_n peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations

Bythell

Molesworth

Osburn

et al. 2008

J. Am. Soc. Mass Spectrom.

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Extensive 15 N labeling and multiple-stage tandem mass spectrometry were used to investigate the fragmentation pathways of the model peptide FGGFL during low-energy collisioninduced-dissociation (CID) in an ion-trap mass spectrometer. Of particular interest was formation of a 4 from b 4 and a 4 * (a 4 -NH 3 ) from a 4 ions correspondingly, and apparent rearrangement and scrambling of peptide sequence during CID. It is suggested that the original FGGF oxa b 4 structure undergoes b-type scrambling to form GGFF oxa . These two isomers fragment further by elimination of CO and 14 NH 3 or 15 NH 3 to form the corresponding a 4 and a 4 * isomers, respectively. For ( 15 N-F)GGFL and FGG( 15 N-F)L the a 4 * ion population appears as two distinct peaks separated by 1 mass unit. These two peaks could be separated and fragmented individually in subsequent CID stages to provide a useful tool for exploration of potential mechanisms along the a 4 ¡ a 4 * pathway reported previously in the literature . In most MS/MS experiments, protonated peptides are excited collisionally to induce dissociation (collision-induced-dissociation, CID) and the fragment ion spectrum is used to elucidate peptide sequences. The CID spectra of peptides in proteomics studies are commonly assigned by bioinformatics tools that implement sequencing algorithms and peptide fragmentation models. Regrettably, the existing sequencing programs are based on rather limited fragmentation models that poorly approximate the rich dissociation chemistry of protonated peptides [3]. These limitations often lead to erroneous assignment of peptides and proteins, and the resulting uncertainty in the evaluation of the raw MS/MS data is one of the major limiting factors in large-scale protein identification studies [4,5]. The incorporation of more detailed peptide fragmentation mechanisms and spectral characteristics into these sequencing algorithms would undoubtedly place MS/MS based sequencing on a much more robust basis.In general, fragmentation of protonated peptides under low-energy collision conditions involves protondriven reactions in which amide bonds are cleaved along the peptide backbone and b, y, and a ions [6,7] are formed. The energetics and kinetics of the necessary proton mobilization (mobile proton model [8,9]) and amide bond cleavage pathways [3, 10 -14] have received significant research interest. On the other hand, much less attention has been devoted to the structure and reactivity of the primary fragments formed by backbone cleavages. According to the recent pathways in competition (PIC) fragmentation model [3], the thermodynamic properties and the reactivity of these fragAddress reprint requests to Dr. M. Van Stipdonk,

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confidence: 87%

Structure and reactivity of a_n and a*_n peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations

Bythell

Molesworth

Osburn

et al. 2008

J. Am. Soc. Mass Spectrom.

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“…The combined quantum chemical and RRKM modeling of the b and y fragmentation mechanisms of protonated model peptides by Paizs and Suhai provides valuable atomic and energetic details for different reaction pathways that may lead to formation of various fragment ions [24,29,30]. Multiple reaction mechanisms such as diketopiperazine, oxazolone, amide O, a 1 -y x , aziridinone pathways [29], and cyclization [18,31,32] imply ion fragmentation via multiple pathways. On the other hand, common reaction pathways have also been suggested for different fragment ions.…”

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H/D exchange kinetics: Experimental evidence for formation of different b fragment ion conformers/isomers during the gas-phase peptide sequencing

Fattahi

Zekavat

Solouki

2010

J. Am. Soc. Mass Spectrom.

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“…After many years of characterization by MS/MS, the study of isomeric gas-phase ion structures has been recently the domain of ion mobility-mass spectrometry (IM-MS) and action IRMPD spectroscopy. Gaskell and coworkers used IM-MS to identify both oxazolone and macrocyclic structures for the b 5 ion from YAGFL-NH 2 , while Clemmer and coworkers used a similar approach to identify linear and macrocyclic structures for the a 4 and b 4 fragment ions from leucine enkephalin [21,22]. Variable wavelength action IRMPD spectroscopy has been recently employed by several research groups for the study of gas-phase ions [23][24][25][26] and has also been the subject of two recent, extensive reviews [27,28].…”

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Separation and identification of structural isomers by quadrupole collision-induced dissociation-hydrogen/deuterium exchange-infrared multiphoton dissociation (QCID-HDX-IRMPD)

Gucinski

Somogyi

Chamot‐Rooke

et al. 2010

J. Am. Soc. Mass Spectrom.

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A new approach that uses a hybrid Q-FTICR instrument and combines quadrupole collisioninduced dissociation, hydrogen-deuterium exchange, and infrared multiphoton dissociation (QCID-HDX-IRMPD) has been shown to effectively separate and differentiate isomeric fragment ion structures present at the same m/z. This method was used to study protonated YAGFL-OH (free acid), YAGFL-NH 2 (amide), cyclic YAGFL, and YAGFL-OCH 3 (methyl ester). QCID-HDX of m/z 552.28 (C 29 T andem mass spectrometry is widely used for the identification of peptides and proteins [1,2]. Generally, protonated peptides at a given m/z are selected and fragmented via collision-induced dissociation (CID), generating 'b' and 'y' fragment ions, which allows the peptide sequence to be determined.In the course of a common proteomics experiment, several hundred to several thousand spectra are generated for a single sample, making manual interpretation of the peptide fragmentation spectra impractical. To speed up the assignment of MS/MS spectra, protein identification algorithms are often used [3,4]. These algorithms generate theoretical peptide spectra or m/z lists based loosely on prevalent fragmentation models, including the mobile proton model [5] and the pathways-in-competition model [6], and compare them with experimental spectra to determine peptide sequences. While these models can help to predict many trends in peptide fragmentation, actual dissociation chemistry is much more complex, and the complete dissociation chemistry in an MS/MS spectrum cannot always be accurately predicted by using existing theoretical models. As a result, false and missed identifications frequently occur, with only a small percentage of the spectra being correctly assigned [7][8][9][10]. Incorporation of additional chemical information and fragmentation models into sequencing algorithms could depict fragmentation processes more completely, potentially allowing more accurate kinetic modeling of spectra to be possible, and the success of identification algorithms would likely improve.One potential cause for missed or false identifications of peptide fragmentation spectra is the presence of multiple isomeric ion structures at a single m/z. If multiple isomers are present at one m/z, the MS/MS spectrum of that m/z could contain fragments from each of the structures present. For example, the b n ions from peptides of length n and the corresponding [MH Ϫ H 2 O] ϩ ions are isomeric. While water loss at the peptide C-terminus results in b 5 ion formation for pentapeptides, water can also be lost involving oxygen from an Address reprint requests to Dr.

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On the Dynamics of Fragment Isomerization in Collision-Induced Dissociation of Peptides

Cited by 84 publications

References 38 publications

Structure and reactivity of a_n and a*_n peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations

Structure and reactivity of a_n and a*_n peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations

H/D exchange kinetics: Experimental evidence for formation of different b fragment ion conformers/isomers during the gas-phase peptide sequencing

Separation and identification of structural isomers by quadrupole collision-induced dissociation-hydrogen/deuterium exchange-infrared multiphoton dissociation (QCID-HDX-IRMPD)

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On the Dynamics of Fragment Isomerization in Collision-Induced Dissociation of Peptides

Cited by 84 publications

References 38 publications

Structure and reactivity of an and a*n peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations

Structure and reactivity of an and a*n peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations

H/D exchange kinetics: Experimental evidence for formation of different b fragment ion conformers/isomers during the gas-phase peptide sequencing

Separation and identification of structural isomers by quadrupole collision-induced dissociation-hydrogen/deuterium exchange-infrared multiphoton dissociation (QCID-HDX-IRMPD)

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Structure and reactivity of a_n and a*_n peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations

Structure and reactivity of a_n and a*_n peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations