Gas Phase Reactivity of Carboxylates with <i>N</i>-Hydroxysuccinimide Esters

Zhou, Peng; McGee, William M.; Bu, Jiexun; Barefoot, Nathan; McLuckey, Scott A.

doi:10.1007/s13361-014-1002-0

Cited by 13 publications

(13 citation statements)

References 32 publications

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“…Examples of gas-phase covalent modification reactions include Schiff base chemistry between amines and aldehydes 11 , Click chemistry between azides and alkenes 12 , and oxidation chemistry between periodate and various reductive groups 13 . A reaction that is particularly useful for protein and peptide modification is the reaction between N -hydroxysuccinimide (NHS) esters and various nucleophiles commonly present in polypeptides such as neutral amines 14 , neutral guanidines 15 , and carboxylates 16 . The reaction involves the covalent attachment of an acyl group to the nucleophile via the displacement of an NHS leaving group, resulting in the formation of an amide on the N-terminal amine or lysine side chain 14 , an N-acyl guanidine on arginine side chains 15 , or an anhydride on the C-terminus or side chain carboxylates 16 .…”

Section: Introductionmentioning

confidence: 99%

Enhanced Reactivity in Nucleophilic Acyl Substitution Ion/Ion Reactions Using Triazole-Ester Reagents

Zhou

Zhao

et al. 2017

J. Am. Soc. Mass Spectrom.

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The acyl substitution reactions between 1-hydroxy-7-aza-benzotriazole (HOAt)/1-hydroxy-benzotriazole (HOBt) ester reagents and nucleophilic side chains on peptides have been demonstrated in the gas phase via ion/ion reactions. The HOAt/HOBt ester reagents were synthesized in solution and ionized via negative nano-electrospray ionization. The anionic reagents were then reacted with doubly protonated model peptides containing amines, guanidines, and imidazoles in the gas phase. The complexes formed in the reaction cell were further probed with ion trap collision induced dissociation (CID) yielding either a covalently modified analyte ion or a proton transfer product ion. The covalent reaction yield of HOAt/HOBt ester reagents was demonstrated to be higher than the yield with N-hydroxysuccinimide (NHS) ester reagents over a range of equivalent conditions. Density functional theory (DFT) calculations were performed with a primary amine model system for both triazole-ester and NHS-ester reactants, which indicated a lower transition state barrier for the former reagent, consistent with experiments. The work herein demonstrates that the triazole-ester reagents are more reactive, and therefore less selective, than the analogous NHS-ester reagent. As a consequence, the triazole-ester reagents are the first to show efficient reactivity with unprotonated histidine residues in the gas phase. For all nucleophilic sites and all reagents, covalent reactions are favored under long time, low amplitude activation conditions. This work presents a novel class of reagents capable of gas-phase conjugation to nucleophilic sites in analyte ions via ion/ion chemistry.

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Section: Introductionmentioning

confidence: 99%

Enhanced Reactivity in Nucleophilic Acyl Substitution Ion/Ion Reactions Using Triazole-Ester Reagents

Zhou

Zhao

et al. 2017

J. Am. Soc. Mass Spectrom.

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“…6,7 Moreover, unique chemistries have been observed via gas-phase ion/ion reactions compared to the solution phase. 7,10 Examples of gas-phase covalent modification reactions include the reactions between N-hydroxysuccinimide (NHS) esters and nucleophiles like primary amines, 11 guanidine groups 12 and carboxylates; 13 gas-phase oxidation of peptides with periodate 14 or persulfate derivatives; 15 carboxylic acid group labelling with carbodiimide reagents; 16 and the Schiff base formation between formyl-benzenesulfonic acids and primary amines. 17 The gas-phase modification of bio-ions via Schiff base formation was first described in 2009.…”

Section: Introductionmentioning

confidence: 99%

Gas‐phase rearrangement reaction of Schiff‐base‐modified peptide ions

Wang

Pilo

Zhao

et al. 2018

Rapid Comm Mass Spectrometry

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Rationale: Schiff base modification of peptides has been shown to facilitate their primary structural characterization via tandem mass spectrometry. However, we have discovered a novel rearrangement reaction via ion trap collisional activation involving the imine of the Schiff base and one of several functional groups, particularly the side-chains of the basic residues lysine, arginine, and histidine, in the peptide. Methods: Gas-phase ion/ion reactions involving an aldehyde-containing reagent were used to generate Schiff-base modified model peptides in a hybrid triple quadrupole/linear ion trap tandem mass spectrometer. Subsequent ion trap collisional activation was used to study the rearrangement reaction. Results: Schiff-base modified peptide ions were found to undergo a rearrangement reaction that was observed to be either a major or minor contributor to the product ion spectrum, depending upon a variety of factors that include, for example, ion polarity, identity of the nucleophile in the peptide (e.g., side-chains of lysine, histidine, and arginine), and the position of the nucleophile relative to the imine. Conclusions: Relatively low energy rearrangement reaction can occur in Schiff base modified peptide ions that involve the imine of the Schiff base and a nucleophile present in the polypeptide. While this rearrangement process does not appear to compromise the structural information that can be generated via collisional activation of Schiff-base-modified peptide ions, it can siphon away signal from the structurally diagnostic processes in some instances.

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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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Gas Phase Reactivity of Carboxylates with N-Hydroxysuccinimide Esters

Cited by 13 publications

References 32 publications

Enhanced Reactivity in Nucleophilic Acyl Substitution Ion/Ion Reactions Using Triazole-Ester Reagents

Enhanced Reactivity in Nucleophilic Acyl Substitution Ion/Ion Reactions Using Triazole-Ester Reagents

Gas‐phase rearrangement reaction of Schiff‐base‐modified peptide ions

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

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