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Gas Phase Reactivity of Carboxylates with N-Hydroxysuccinimide Esters

  • Research Article
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Journal of The American Society for Mass Spectrometry

Abstract

N-hydroxysuccinimide (NHS) esters have been used for gas-phase conjugation reactions with peptides at nucleophilic sites, such as primary amines (N-terminus, ε-amine of lysine) or guanidines, by forming amide bonds through a nucleophilic attack on the carbonyl carbon. The carboxylate has recently been found to also be a reactive nucleophile capable of initiating a similar nucleophilic attack to form a labile anhydride bond. The fragile bond is easily cleaved, resulting in an oxygen transfer from the carboxylate-containing species to the reagent, nominally observed as a water transfer. This reactivity is shown for both peptides and non-peptidic species. Reagents isotopically labeled with O18 were used to confirm reactivity. This constitutes an example of distinct differences in reactivity of carboxylates between the gas phase, where they are shown to be reactive, and the solution phase, where they are not regarded as reactive with NHS esters.

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Acknowledgments

The authors thank Dr. Mingji Dai for helpful discussions on a potential gas-phase scrambling mechanism of the anhydride. This work was supported by the National Institutes of Health under grant GM 45372.

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Authors and Affiliations

  1. Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907-2084, USA

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

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  1. Zhou Peng
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  2. William M. McGee
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  3. Jiexun Bu
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  4. Nathan Z. Barefoot
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  5. Scott A. McLuckey
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Correspondence to Scott A. McLuckey.

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Peng, Z., McGee, W.M., Bu, J. et al. Gas Phase Reactivity of Carboxylates with N-Hydroxysuccinimide Esters. J. Am. Soc. Mass Spectrom. 26, 174–180 (2015). https://doi.org/10.1007/s13361-014-1002-0

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  • DOI: https://doi.org/10.1007/s13361-014-1002-0

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