Covalent and non‐covalent binding in the ion/ion charge inversion of peptide cations with benzene‐disulfonic acid anions

Stutzman, John R.; Luongo, Carl A.; McLuckey, Scott A.

doi:10.1002/jms.2968

Cited by 20 publications

(47 citation statements)

References 45 publications

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“…39–43 This chemistry, as demonstrated in Figure S1, proceeds via the formation of long-lived electrostatic complexes arising from noncovalent interactions between the sulfonate moieties of FBDSA reagent anions and protonated sites of peptide cations. 40 Subsequent collisional activation of these ion/ion intermediates promotes nucleophilic attack on the FBDSA aldehyde by an unprotonated primary amine in the substrate peptide, resulting in concerted dehydration and imine bond formation.…”

Section: Resultsmentioning

confidence: 99%

Modulation of Phosphopeptide Fragmentation via Dual Spray Ion/Ion Reactions Using a Sulfonate-Incorporating Reagent

2016

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The labile nature of phosphoryl groups has presented a long-standing challenge for the characterization of protein phosphorylation via conventional mass spectrometry-based bottom-up proteomics methods. Collision-induced dissociation (CID) causes preferential cleavage of the phospho-ester bond of peptides, particularly under conditions of low proton mobility, and results in the suppression of sequence-informative fragmentation that often prohibits phosphosite determination. In the present study, the fragmentation patterns of phosphopeptides are improved through ion/ion-mediated peptide derivatization with 4-formyl-1,3-benezenedisulfonic acid (FBDSA) anions using a dual spray reactor. This approach exploits the strong electrostatic interactions between the sulfonate moieties of FBDSA and basic sites to facilitate gas-phase bioconjugation and to reduce charge sequestration and increase the yield of phosphate-retaining sequence ions upon CID. Moreover, comparative CID fragmentation analysis between unmodified phosphopeptides and those modified online with FBDSA or in solution via carbamylation and 4-sulfophenyl isothiocyanate (SPITC) provided evidence for sulfonate interference with charge-directed mechanisms that result in preferential phosphate elimination. Our results indicate the prominence of charge-directed neighboring group participation reactions involved in phosphate neutral loss, and the implementation of ion-ion reactions in a dual spray reactor set-up provides a means to disrupt the interactions by competing hydrogen-bonding interactions between sulfonate groups and the side-chains of basic residues.

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Section: Resultsmentioning

confidence: 99%

Modulation of Phosphopeptide Fragmentation via Dual Spray Ion/Ion Reactions Using a Sulfonate-Incorporating Reagent

2016

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“…The C-terminus apparently enhances the reactivity of the [ac-AKAAARA+2Na] 2+ ion (◊ H/Na /X H/Na > 20) whereas it apparently diminishes the reactivity of the [ac-ARAAAKA+2Na] 2+ ion (◊ H/Na /R H/Na ≈ 0.6). It has previously been proposed that an intramolecular interaction between the carboxyl-terminus and protonated arginine exists when the arginine residue is located near the C-terminal end of the peptide [38]. More specifically, spectroscopic studies indicate that sodium cationized arginine exists in a zwitterionic state in which the protonated arginine side chain donates one hydrogen bond to the N-terminus and the sodium ion is bicoordinated with the C-terminal carboxylate group whereas protonated arginine existed only in a nonzwitterionic form.…”

Section: Resultsmentioning

confidence: 99%

Strategies for the gas phase modification of cationized arginine via ion/ion reactions

Prentice

McGee

Stutzman

et al. 2013

International Journal of Mass Spectrometry

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The gas phase acetylation of cationized arginine residues is demonstrated here using ion/ion reactions with sulfosuccinimidyl acetate (sulfo-NHS acetate) anions. Previous reports have demonstrated the gas phase modification of uncharged primary amine (the N-terminus and ε-amino side chain of lysine) and uncharged guanidine (the arginine side chain) functionalities via sulfo-NHS ester chemistry. Herein, charge-saturated arginine-containing peptides that contain sodium ions as the charge carriers, such as [ac-ARAAARA+2Na]2+, are shown to exhibit strong reactivity towards sulfo-NHS acetate whereas the protonated peptide analogues exhibit no such reactivity. This difference in reactivity is attributed to the lower sodium ion (as compared to proton) affinity of the arginine, which results in increased nucleophilicity of the cationized arginine guanidinium functionality. This increased nucleophilicity improves the arginine residue's reactivity towards sulfo-NHS esters and enhances the gas phase covalent modification pathway. No such dramatic increase in reactivity towards sulfo-NHS acetate has been observed upon sodium cationization of lysine amino acid residues, indicating that this behavior appears to be unique to arginine. The sodium cationization process is demonstrated in the condensed phase by simply spiking sodium chloride into the peptide sample solution and in the gas phase by a peptide-sodium cation exchange process with a sulfo-NHS acetate sodium-bound dimer cluster reagent. This methodology demonstrates several ways by which arginine can be covalently modified in the gas phase even when it is charged. Collisional activation of an acetylated arginine product can result in deguanidination of the residue, generating an ornithine. This gas phase ornithination exhibits similar site-specific fragmentation behavior to that observed with peptides ornithinated in solution and may represent a useful approach for inducing selective peptide cleavages.

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“…Recently, ion/ion complex formation has been used for gas covalent modifications[22]. The covalent reactions have included such examples as gas phase Schiff base formation [22, 23], modification of amines with NHS-ester chemistry [24, 25], reactions with carboxylic acids [26, 27], and gas phase oxidations of disulfide bonds [28, 29]. Ion/ion reactions are showing great promise in moving site-specific traditionally solution phase bio-conjugation reactions into the gas phase.…”

Section: Introductionmentioning

confidence: 99%

Design of a TW-SLIM Module for Dual Polarity Confinement, Transport, and Reactions

Garimella

Webb

Prabhakaran

et al. 2017

J. Am. Soc. Mass Spectrom.

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Here we describe instrumental approaches for performing dual polarity ion confinement, transport, ion mobility separations and reactions in Structures for Lossless Ion Manipulations (SLIM). Previous means of ion confinement in SLIM based upon rf- generated pseudopotentials and dc fields for lateral confinement cannot trap ions of opposite polarity simultaneously. Here we explore alternative approaches to provide lateral confinement of both ion polarities. Traveling wave ion mobility (IM) separations experienced by both polarities in such SLIM cause ions of both polarities to migrate in the same directions and exhibit similar separations. The ion motion (and relative motion of the two polarities) under both surfing and IM separation conditions are discussed. In surfing conditions, where the traveling wave speed is less than the ion velocity, the two polarities are transported losslessly and non-reactively in their respective potential minima (higher absolute voltage regions confines negative polarities and lower absolute potential regions are populated by positive polarities). In separation mode, where the traveling wave speed is greater than the ion velocity, the two polarities can interact during rollovers over the traveling wave. Strategies to minimize overlap of the two ion populations to prevent reactive losses during separations are presented. A theoretical treatment of the time scales over which two populations (injected into a dc field-free region of the dual polarity SLIM device) interact is considered, and SLIM designs for allowing ion/ion interactions and other manipulations with dual polarities at 4 torr are presented.

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Covalent and non‐covalent binding in the ion/ion charge inversion of peptide cations with benzene‐disulfonic acid anions

Cited by 20 publications

References 45 publications

Modulation of Phosphopeptide Fragmentation via Dual Spray Ion/Ion Reactions Using a Sulfonate-Incorporating Reagent

Modulation of Phosphopeptide Fragmentation via Dual Spray Ion/Ion Reactions Using a Sulfonate-Incorporating Reagent

Strategies for the gas phase modification of cationized arginine via ion/ion reactions

Design of a TW-SLIM Module for Dual Polarity Confinement, Transport, and Reactions

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