Transformation of [M+2H]2+ Peptide Cations to [M – H]+, [M+H+O]+, and M+• Cations via Ion/Ion Reactions: Reagent Anions Derived from Persulfate

Pilo, Alice L.; Bu, Jiexun; McLuckey, Scott A.

doi:10.1007/s13361-015-1125-y

Cited by 10 publications

(22 citation statements)

References 60 publications

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“…39,40 For the reactions shown here, these reagents are, for the most part, interchangeable. As the stronger oxidizing agent of the two, persulfate tends to lead to more reactive pathways than periodate.…”

Section: Resultsmentioning

confidence: 99%

Selective Gas-Phase Ion/Ion Reactions: Enabling Disulfide Mapping via Oxidation and Cleavage of Disulfide Bonds in Intermolecularly-Linked Polypeptide Ions

Pilo

McLuckey

2016

Anal. Chem.

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The selective gas-phase oxidation of disulfide bonds to their thiosulfinate form using ion/ion reactions and subsequent cleavage is demonstrated here. Oxidizing reagent anions are observed to attach to all polypeptides, regardless of amino acid composition. Direct proton transfer yielding a charge-reduced peptide is also frequently observed. Activation of the ion/ion complex between an oxidizing reagent anion and a disulfide-containing peptide cation results in oxygen transfer from the reagent anion to the peptide cation to form the [M +H+O]+ species. This thiosulfinate derivative can undergo one of several rearrangements that result in cleavage of the disulfide bond. Species containing an intermolecular disulfide bond undergo separation of the two chains upon activation. Further activation can be used to generate more sequence information from each chain. These oxidation ion/ion reactions have been used to illustrate the identification of S-glutathionylated and S-cysteinylated peptides, in which low molecular weight thiols are attached to cysteine residues in peptides via disulfide bonds. The oxidation chemistry effectively labels peptide ions with readily oxidized groups, such as disulfide bonds. This enables a screening approach for the identification of disulfide-linked peptides in a disulfide mapping application involving enzymatic digestion. The mixtures of ions generated by tryptic and peptic digestions of lysozyme and insulin, respectively, without prior separation or isolation were subjected both to oxidation and proton transfer ion/ion chemistry to illustrate the identification of peptides in the mixtures with readily oxidized groups.

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Section: Resultsmentioning

confidence: 99%

Selective Gas-Phase Ion/Ion Reactions: Enabling Disulfide Mapping via Oxidation and Cleavage of Disulfide Bonds in Intermolecularly-Linked Polypeptide Ions

Pilo

McLuckey

2016

Anal. Chem.

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“…Nevertheless, possible mechanisms for the oxidation of neutral arginine and lysine side-chains to the [M-H] + species are provided in Scheme 2. Similar to the mechanisms proposed for the generation of the same species via ion/ion reactions with persulfate anion [26], the reaction proceeds via abstraction of two hydrogen atoms from adjacent carbon and nitrogen atoms with concurrent proton transfer from the peptide cation to the reagent anion. The hydrogen atoms abstracted in Scheme 2 were chosen because they had the lowest reported local bond dissociation energies [32].…”

Section: Resultsmentioning

confidence: 86%

“…Furthermore, the oxidation of protonated polypeptides to [M+H+O] + , [M-H] + , and M +• species upon ion/ion reactions with a suite of reagents derived from persulfate has been demonstrated [26]. These oxidation ion/ion reactions have been used to determine which cysteine residues are involved in disulfide bonds, identify and localize certain post-translational modifications (e.g., prenylation), and obtain additional primary structural information.…”

Section: Introductionmentioning

confidence: 99%

Gas-Phase Oxidation of Neutral Basic Residues in Polypeptide Cations by Periodate

Pilo

McLuckey

2016

J. Am. Soc. Mass Spectrom.

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The gas-phase oxidation of doubly protonated peptides containing neutral basic residues to various products, including [M+H+O]+, [M-H]+, and [M-H-NH3]+, is demonstrated here via ion/ion reactions with periodate. It was previously demonstrated that periodate anions are capable of oxidizing disulfide bonds and methionine, tryptophan, and S-alkyl cysteine residues. However, in the absence of these easily oxidized sites, we show here that systems containing neutral basic residues can undergo oxidation. Furthermore, we show that these neutral basic residues primarily undergo different types of oxidation (e.g., hydrogen abstraction) reactions than those observed previously (i.e., oxygen transfer to yield the [M+H+O]+ species) upon gas-phase ion/ion reactions with periodate anions. This chemistry is illustrated with a variety of systems including a series of model peptides, a cell-penetrating peptide containing a large number of unprotonated basic sites, and ubiquitin, a roughly 8.6 kDa protein.

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“…Furthermore, the oxidation of peptides to [M + H + O] + , [M − H] + , and M +• species via reaction with a suite of reagents derived from persulfate has been demonstrated. 48 Here, we extend the approach used to oxidize methionine to S-alkyl cysteine residues because they are similar in structure. The solution-phase oxidation of various S-alkyl cysteine residues has been investigated previously and can also undergo rearrangement upon activation to lose the alkyl sulfenic acid.…”

Section: Introductionmentioning

confidence: 99%

Selective Gas-Phase Oxidation and Localization of Alkylated Cysteine Residues in Polypeptide Ions via Ion/Ion Chemistry

2016

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The thiol group in cysteine residues is susceptible to several post-translational modifications (PTMs), including prenylation, nitrosylation, palmitoylation, and the formation of disulfide bonds. Additionally, cysteine residues involved in disulfide bonds are commonly reduced and alkylated prior to mass spectrometric analysis. Several of these cysteine modifications, specifically S-alkyl modifications, are susceptible to gas-phase oxidation via selective ion/ion reactions with periodate anions. Multiply protonated peptides containing modified cysteine residues undergo complex formation upon ion/ion reaction with periodate anions. Activation of the ion/ion complexes results in oxygen transfer from the reagent to the modified sulfur residue to create a sulfoxide functionality. Further activation of the sulfoxide derivative yields abundant losses of the modification with the oxidized sulfur as a sulfenic acid (namely, XSOH) to generate a dehydroalanine residue. This loss immediately indicates the presence of an S-alkyl cysteine residue, and the mass of the loss can be used to easily deduce the type of modification. An additional step of activation can be used to localize the modification to a specific residue within the peptide. Selective cleavage to create c- and z-ions N-terminal to the dehydroalanine residue is often noted. As these types of ions are not typically observed upon collision-induced dissociation (CID), they can be used to immediately indicate where in the peptide the PTM was originally located.

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Transformation of [M+2H]²⁺ Peptide Cations to [M – H]⁺, [M+H+O]⁺, and M^+• Cations via Ion/Ion Reactions: Reagent Anions Derived from Persulfate

Cited by 10 publications

References 60 publications

Selective Gas-Phase Ion/Ion Reactions: Enabling Disulfide Mapping via Oxidation and Cleavage of Disulfide Bonds in Intermolecularly-Linked Polypeptide Ions

Selective Gas-Phase Ion/Ion Reactions: Enabling Disulfide Mapping via Oxidation and Cleavage of Disulfide Bonds in Intermolecularly-Linked Polypeptide Ions

Gas-Phase Oxidation of Neutral Basic Residues in Polypeptide Cations by Periodate

Selective Gas-Phase Oxidation and Localization of Alkylated Cysteine Residues in Polypeptide Ions via Ion/Ion Chemistry

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