Aspartic acid side chain effect—Experimental and theoretical insight

Rožman, Marko

doi:10.1016/j.jasms.2006.09.009

Cited by 37 publications

(36 citation statements)

References 21 publications

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“…This observation suggests that despite Coulombic repulsion, y ion provides better charge solvation shell for the sodium cation and thus possesses higher sodium affinity. This is consistent with the rigidity of cyclic anhydride structure proposed for b-type ions formed by the aspartic acid effect [30] which will be especially pronounced for the smallest b ion.…”

Section: Influence Of Peptide Primary Structuresupporting

confidence: 90%

“…Interestingly, estimated magnitude of K + and Rb + bond dissociation energies (100-150 kJ mol −1 ) lies around threshold for Asp effect; which is 100-130 kJ mol −1 for unhindered Asp side chain. [30] Thus, this comparison could explain why for rubidated peptides metal expulsion becomes a dominant process.…”

Section: Molecular Modelling and Theoretical Cross Sectionsmentioning

confidence: 97%

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

Rožman

Gaskell

2010

J. Mass Spectrom.

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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.

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Section: Influence Of Peptide Primary Structuresupporting

confidence: 90%

Section: Molecular Modelling and Theoretical Cross Sectionsmentioning

confidence: 97%

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

Rožman

Gaskell

2010

J. Mass Spectrom.

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“…The major fragment ion resulting in loss of residue masses is the ion at m/z 350, which corresponds to the loss of both phenylalanine and leucine, and appears at about 60% relative intensity. This fragment ion could be explained as a direct sequence fragment (b 3 ϩ ), and can be attributed to the "aspartic acid effect" invoked in other, earlier studies [29,30,35,36]. For peptides with acidic residues, attack by the side chain is proposed to result in formation of a cyclic anhydride at the C-terminal end of a product ion, and, in the case of the opening of the putative macro-cycle, this would more than likely be the case.…”

Section: Resultsmentioning

confidence: 53%

Influence of amino acid side chains on apparent selective opening of cyclic b₅ ions

Molesworth

Osburn

Stipdonk

2010

J. Am. Soc. Mass Spectrom.

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In this study, the possible influence of acidic, basic, and amide side chains on the opening of a putative macrocyclic b ion (b 5 ϩ ) intermediate was investigated. Collision induced dissociation (CID) of b 5 ions was studied using a group of hexapeptides in which amino acids with the side chains of interest occupied internal sequence positions. Further experiments were performed with permuted isomers of glutamine (Q) containing peptides to probe for sequence scrambling and whether the specific sequence site of the residues influences opening of the macrocycle. Overall, the trend for (apparent) preferential/selective opening of the cyclic b 5 ϩ , presumably due to the side chain, followed by the loss of the amino acid with active side group is: [3], is dependent, in part, on product ion distributions generated by CID. For bioinformatics approaches in particular, prediction of fragmentation patterns often employs rules that are rudimentary and simple. This may lead to invalid assignments of peptide and protein identity [3,4]. Certainly, a better understanding of fundamental gas-phase peptide fragmentation chemistry and physics would potentially lead to enhanced and more accurate bioinformatics-based MS/MS sequencing.Using low-energy collision induced dissociation (CID), fragmentation of protonated peptides traditionally involves charge (proton) mediated reactions, with induced cleavage of amide bonds leading to the generation of b, y, and a ions [5,6]. Development of the mobile proton model [7,8] of peptide fragmentation, and related amide bond cleavage pathways [9 -14], has been focused on the energetics and kinetics of proton mobilization. The more recent pathways in competition (PIC) fragmentation model [14] uses the mobile proton model as a foundation for understanding, but takes into account the structures and reactivity of key reactive configurations and primary fragments as well as transition states and their energies.There is a great deal of evidence that N-terminal b n type fragment ions have structures that include, at least in part, C-terminal oxazolone rings [9,15], and retain much of the primary sequence of the precursor peptide ion. However, more recent experiments [16 -19] strongly suggest that a macro-cyclic b ion isomer, or intermediate, can arise through cyclization of the linear, oxazolone-terminated b ions; this macrocyclic species can then open at different amide bonds to regain a linear, oxazolone terminated structure. One problematic outcome of such a cyclization and reopening process is the associated scrambling of the original primary sequence. This type of pathway is referred to as b-type scrambling of peptide fragment ions [16]. Above and beyond the "head to tail" type formation of the macrocycle, there exist several other possible processes that could play a significant role in the scrambling of sequence, the majority of which involve opening of the cyclic b ion. For example, peptides that contain acidic, basic, and amide side amino acids feature side chains that can serve as nucleo...

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“…Both the small model system and the peptides were optimised at the B3LYP/6-31G(d) level of theory. Both the functional and the basis set represent a good compromise for obtaining satisfactory geometries and approximate relative energies, as demonstrated in the theoretical studies of similar systems [7,19,20]. Stationary points (i.e.…”

Section: Methodsmentioning

confidence: 99%

Study of the gas-phase fragmentation behaviour of sulfonated peptides

Škulj

Rožman

2015

International Journal of Mass Spectrometry

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a b s t r a c tA series of singly and doubly protonated peptides bearing sulfonated residue have been studied, using both experiment and molecular modelling, to elucidate fragmentation chemistry of sulfonated peptides. Collision-induced dissociation mass spectra indicate that the sulfo group loss (neutral loss of 80 Da) is the dominant dissociation channel. Modelling results suggest the proton transfer mechanism, where upon vibrational excitation, the acidic side chain proton is transferred from the sulfo group hydroxyl to the ester oxygen resulting in S O bond cleavage and formation of the unmodified hydroxyl containing residue and SO 3 . Conformations associated with potential energy profile of the reaction imply the charge remote nature of the proposed mechanism. The proposed proton transfer mechanism was compared with the intramolecular nucleophilic substitution (S N 2) mechanism, the main pathway suggested for neutral loss of phosphoric acid from phosphopeptides. Both pathways (proton transfer and S N 2) are available for sulfonated and phosphorylated peptides; however, each posttranslational modification favours different mechanism. The change of the bond dissociation enthalpies and the ability of stabilising the transition state structures are demonstrated as main factors responsible for each posttranslational modification activating a different pathway.

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Aspartic acid side chain effect—Experimental and theoretical insight

Cited by 37 publications

References 21 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

Influence of amino acid side chains on apparent selective opening of cyclic b₅ ions

Study of the gas-phase fragmentation behaviour of sulfonated peptides

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Aspartic acid side chain effect—Experimental and theoretical insight

Cited by 37 publications

References 21 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

Influence of amino acid side chains on apparent selective opening of cyclic b5 ions

Study of the gas-phase fragmentation behaviour of sulfonated peptides

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Influence of amino acid side chains on apparent selective opening of cyclic b₅ ions