Gas-Phase Conjugation to Arginine Residues in Polypeptide Ions via N -Hydroxysuccinimide Ester-Based Reagent Ions

J. Am. Soc. Mass Spectrom.

McLuckey

2015

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The gas-phase oxidation of doubly protonated peptides is demonstrated here using ion/ion reactions with a suite of reagents derived from persulfate. Intact persulfate anion (HS2O8−), peroxymonosulfate anion (HSO5−), and sulfate radical anions (SO4−•) are all either observed directly upon negative nanoelectrospray ionization (nESI) or easily obtained via beam-type collisional activation of persulfate into the mass spectrometer. Ion/ion reactions between each of these reagents and doubly protonated peptides results in formation of a long-lived complex. Collisional activation of the complex containing a peroxymonosulfate anion results in oxygen transfer from the reagent to the peptide to generate the [M+H+O]+ species. Activation of the complex containing intact persulfate anion either results in oxygen transfer to generate the [M+H+O]+ species or abstraction of two hydrogen atoms and a proton to generate the [M-H]+ species. Activation of the complex containing sulfate radical anion results in abstraction of one hydrogen atom and a proton to form the peptide radical cation, [M]+•. This suite of reagents allows for the facile transformation of the multiply protonated peptides obtained via nESI into a variety of oxidized species capable of providing complementary information about the sequence and structure of the peptide.

Section: Introductionmentioning

confidence: 99%

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

J. Am. Soc. Mass Spectrom.

McLuckey

2015

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“…Aside from these charged particle transfer reactions, a number of approaches to covalently modify ions via a long-lived complex in the gas-phase have been developed, aiming at selectively manipulating ion types at specific functionalities. For example, N -hydroxysuccinimide (NHS) and sulfo-NHS ester-based reagents have been used to covalently modify primary amines (N-terminus, lysine side chain) 13 and guanidines 14,15 on arginine side chains by forming amide bonds via ion/ion reactions. Similarly, the formation of imine bonds (i.e., Schiff base formation) with primary amines using 4-formyl-1,3-benzenedisulfonic acid (FBDSA) dianions has been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

“…19 These specific covalent modifications of peptides and proteins via ion/ion reactions have been used to tag peptides and proteins with chromophores, 20 cross-link peptides and proteins, 2122 and increase sequence information upon collisional activation. 23 In addition, some reaction products observed in these gas-phase reactions are not typically observed in solution, 14,19 providing exclusive access to novel fragmentation patterns.…”

Section: Introductionmentioning

confidence: 99%

Gas-Phase Amidation of Carboxylic Acids with Woodward’s Reagent K Ions

Zhou

J. Am. Soc. Mass Spectrom.

Luongo

et al. 2015

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Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward’s reagent K (wrk) in both positive and negative mode. Woodward’s reagent K, N-ethyl-3-phenylisoxazolium-3′-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

“…An example of covalent modification in the gas phase is Schiff base formation between formyl-benzenesulfonic acids and primary amine groups on peptides [16]. Reactions between N-hydroxysuccinimide esters and a nucleophile, such as a primary amine [17], a guanidine group [18], and a carboxylate [19], have also been described. The covalent labeling of carboxylic acid groups was achieved via ion/ion reactions with carbodiimide reagents [20].…”

Section: Introductionmentioning

confidence: 99%

Gas phase click chemistry via ion/ion reactions

International Journal of Mass Spectrometry

McLuckey

2015

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a b s t r a c tThe 1,3-dipolar cycloaddition between azides and alkynes, i.e., 'click' chemistry, has been demonstrated in the gas phase via ion/ion reactions. Doubly protonated azide-modified peptide cations were reacted with singly deprotonated dibenzoazacyclooctyne DIBAC reagent anions to form a long-lived complex monocation. Similarly, ion/ion complex monoanions were generated in the negative mode via reactions between singly protonated azide-containing cations and doubly deprotonated DIBAC reagent anions. Activation of ion/ion complexes in either polarity resulted in the formation of a triazole, a covalent linkage that can be further probed via MS n . The click chemistry coupled species synthesized in solution and subsequently transferred into the gas phase yielded the same products as those synthesized in gas phase when activated in the mass spectrometer. Analogous click chemistry products were synthesized in the solution phase and activated via tandem mass spectrometry as a control for the dissociation of the novel gas-phase reaction products. Density functional theory (DFT) calculations were performed to provide estimates for key processes (e.g., reaction barriers and energies) that can occur in the overall reaction. The work herein demonstrates that it is possible to conjugate azide and alkyne functional groups in the gas-phase, and represents another example of the growing number of selective covalent reactions that can take place via gas-phase ion/ion reactions.