Fragmentation pathways of protonated peptides

Paizs, Béla; Suhai, Sándor

doi:10.1002/mas.20024

Cited by 986 publications

(1,040 citation statements)

References 106 publications

Supporting

Mentioning

1,000

Contrasting

Unclassified

Order By: Relevance

“…Observed fragment ions suggest that the loss of water is from the Glu 1 residue. Similar behaviour was observed for singly charged (no basic residues, proton on N-terminal nitrogen) peptides containing Glu at the N-terminus [27,28] (Scheme 1(a)). In our case the ionising proton is most likely to be located on the arginine side chain suggesting that the neutral N-terminal Glu can exhibit expulsion of water, (Scheme 1(b)).…”

Section: Molecular Modelling and Theoretical Cross Sectionssupporting

confidence: 72%

Non‐covalent interactions of alkali metal cations with singly charged tryptic peptides

Rožman

Gaskell

2010

J. Mass Spectrom.

View full text Add to dashboard Cite

The complexes formed by alkali metal cations (Cat + = Li + ,Na + ,K + ,Rb + ) and singly charged tryptic peptides were investigated by combining results from the low-energy collision-induced dissociation (CID) and ion mobility experiments with molecular dynamics and density functional theory calculations. The structure and reactivity of [M+H +Cat] 2+ tryptic peptides is greatly influenced by charge repulsion as well as the ability of the peptide to solvate charge points. Charge separation between fragment ions occurs upon dissociation, i.e. b ions tend to be alkali metal cationised while y ions are protonated, suggesting the location of the cation towards the peptide N-terminus. The low-energy dissociation channels were found to be strongly dependant on the cation size. Complexes containing smaller cations (Li + or Na + ) dissociate predominantly by sequence-specific cleavages, whereas the main process for complexes containing larger cations (Rb + ) is cation expulsion and formation of [M + H] + . The obtained structural data might suggest a relationship between the peptide primary structure and the nature of the cation coordination shell. Peptides with a significant number of side chain carbonyl oxygens provide good charge solvation without the need for involving peptide bond carbonyl groups and thus forming a tight globular structure. However, due to the lack of the conformational flexibility which would allow effective solvation of both charges (the cation and the proton) peptides with seven or less amino acids are unable to form sufficiently abundant [M+H+Cat] 2+ ion. Finally, the fact that [M+H+Cat] 2+ peptides dissociate similarly as [M + H] + (via sequence-specific cleavages, however, with the additional formation of alkali metal cationised b ions) offers a way for generating the low-energy CID spectra of 'singly charged' tryptic peptides.

show abstract

Section: Molecular Modelling and Theoretical Cross Sectionssupporting

confidence: 72%

Non‐covalent interactions of alkali metal cations with singly charged tryptic peptides

Rožman

Gaskell

2010

J. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

“…Alternatively, proton transfer from the cation A to Me 3 N may precede the separation of the IMC, which then results in the formation of the trimethylammonium ion, a product ion observed in the CID spectrum of ACh. Intermolecular proton transfer within ionmolecule complexes is a common and important process during the fragmentation of protonated amino acids and peptides, which has been proposed to occur with a negligible energy barrier depending on the relative proton affinity (PA) of the individual neutral species [30]. In the present example, transfer of a proton from the exocyclic OCH 3 group to trimethylamine followed by dissociation is only marginally more endothermic (0.7 kcal mol Ϫ1 ) than dissociation without proton transfer.…”

Section: Dft Calculations Of the Competing Fragmentation Pathways Of mentioning

confidence: 81%

How does acetylcholine lose trimethylamine? A density functional theory study of four competing mechanisms

Lioe

Barlow

O’Hair

2009

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Low-energy collision-induced dissociation (CID) of acetylcholine (ACh) yields only two fragment ions: the dominant C 4 H 7 O 2 ϩ ion at m/z 87, arising from trimethylamine loss; and protonated trimethylamine at m/z 60. Since the literature is replete with conflicting mechanisms for the loss of trimethylamine from ACh, in this article density functional theory (DFT) calculations are used to assess four competing mechanisms: (1) Path A involves a neighboring group attack to form a five-membered ring product, 2-methyl-1,3-dioxolan-2-ylium cation; (2) Path B is a neighboring group attack to form a three-membered ring product, 1-methyloxiranium ion; (3) Path C involves an intramolecular elimination reaction to form C¢O protonated vinylacetate; and (4) Path D is a 1,2-hydride migration reaction forming CH 2 -protonated vinylacetate. At the MP2/6-311ϩϩG(2d,p)//B3-LYP/6-31ϩG(d,p) level of theory path A is the kinetically favored pathway, with a transition-state energy barrier of 37.7 kcal mol Ϫ1 relative to the most stable conformer of ACh. The lowest energy pathway for the formation of protonated trimethylamine was also calculated to proceed via path A, involving proton transfer within the ion-molecule complex intermediate, with the exocylic methyl group being the proton donor. To confirm the site of proton transfer, low-energy CID of acetyl-d 3 -choline (d 3 -ACh) was carried out, which revealed loss of trimethylamine and the formation of Me 3 ND ϩ . (J Am Soc Mass Spectrom 2009, 20, 238 -246)

show abstract

“…For example, some groups have reported that certain peptides show enhanced cleavage at special amino acid residues to produce incomplete sequence information [15]. Hence, the study on fragmention intensity relationship was of further concern and specially reviewed by Paizs and Suhai [16]. Also, another class of anomalous fragmentations introduced in this paper should receive attention.…”

mentioning

confidence: 90%

“…Therefore, if a Pro residue is relocated at the C-terminus of the rearranged a n * ion, the amide bond Xxx-Pro will be preferred to cleave via the b n ¡b n-1 pathway to form an a n *ϪP ion (Pathway III), driving the reversible reaction toward right orientation (Pathway I). On the basisüofütheü"pathwaysüinücompetition"ümodelü [16],üthe ring-opening pathways of the CPI are competitive. As a result, the amide bond Pro-Xxx in CPI is preferred to dissociate.…”

Section: Evidence To Support the Proposed Mechanism For B-type Ionsmentioning

confidence: 99%

“…In addition, structural elucidations of natural or synthetic peptides, including linear peptides [7,8], cyclic peptides [9,10], and peptide analogues [11] also rely on MS/MS analysis. Undoubtedly, all of the applications described above are based on understanding the dissociation mechanisms of peptides, which have been well summarized in recent reviews [12][13][14][15][16]. However, conventional knowledge of fragmentation pathways and rules cannot reasonably explain many anomalous fragmentations.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cyclization reaction of peptide fragment ions during multistage collisionally activated decomposition: An inducement to lose internal amino-acid residues

Jia

2007

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

During characterization of some peptides (linear precursors of the cyclic peptides showing potential to be anticancer drugs) in an ion trap, it was noted that many internal amino acid residues could be lost from singly charged b ions. The phenomenon was not obvious at the first stage of collisionally activated decomposition (CAD), but was apparent at multiple stages of CAD. The unique fragmentation consisting of multiple steps is induced by a cyclization reaction of b ions, the mechanism of which has been probed by experiments of N-acetylation, MS n , rearranged-ion design, and activation-time adjustment. The fragmentation of synthetic cyclic peptides demonstrates that a cyclic peptide intermediate (CPI) formed by b ion cyclization exhibits the same fragmentation pattern as a protonated cyclic peptide. Although no rules for the cyclization reaction were discerned in the experiments of peptide modification, the fragmentations of a number of b ions indicate that the "Pro and Asn/Gln effects" can influence ring openings of CPIs. In addition, large-scale losses of internal residues from different positions of a-type ions have been observed when pure helium was used as collision gas. The fragmentation is initiated by a cyclization reaction forming an a-type ion CPI. This CPI with a fixed-charge structure cannot be influenced by the "Pro effect", causing a selective ring opening at the amide bond Pro-Xxx rather than Xxx-Pro. With the knowledge of the unique fragmentations leading to internal residue losses, the misidentification of fragments and sequences of peptides may be avoided. [5,6] sequencings. For the top-down sequencing, the protein sample without enzymatic digestion is transferred into the gas phase intact, which has the potential for 100% sequence coverage of the protein and improved detection of post-translational modifications [4]. The bottom-up sequencing requires MS/MS analysis of the proteolytic fragments and database searching using algorithms such as Mascot and Sequest [5,6]. In addition, structural elucidations of natural or synthetic peptides, including linear peptides [7,8], cyclic peptides [9,10], and peptide analogues [11] also rely on MS/MS analysis. Undoubtedly, all of the applications described above are based on understanding the dissociation mechanisms of peptides, which have been well summarized in recent reviews [12][13][14][15][16]. However, conventional knowledge of fragmentation pathways and rules cannot reasonably explain many anomalous fragmentations. For example, some groups have reported that certain peptides show enhanced cleavage at special amino acid residues to produce incomplete sequence information [15]. Hence, the study on fragmention intensity relationship was of further concern and specially reviewed by Paizs and Suhai [16]. Also, another class of anomalous fragmentations introduced in this paper should receive attention.For peptide sequencing, the ideal fragmentation pattern of peptides is that the amino acid residues are sequentially lost from the C/N-terminus. However,...

show abstract

Fragmentation pathways of protonated peptides

Cited by 986 publications

References 106 publications

Non‐covalent interactions of alkali metal cations with singly charged tryptic peptides

Non‐covalent interactions of alkali metal cations with singly charged tryptic peptides

How does acetylcholine lose trimethylamine? A density functional theory study of four competing mechanisms

Cyclization reaction of peptide fragment ions during multistage collisionally activated decomposition: An inducement to lose internal amino-acid residues

Contact Info

Product

Resources

About