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A mass spectrometric and ab initio study of the pathways for dehydration of simple glycine and cysteine-containing peptide [M+H]+ ions

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Journal of the American Society for Mass Spectrometry

Abstract

The gas phase fragmentation reactions of the [M+H]+ and [M+H−H2O]+ ions of glycylglycine, glycylcysteine, N-acetylglycine, N-acetylcysteine, their corresponding methyl esters, as well as several other related model systems have been examined by electrospray ionization (ESI) tandem mass spectrometry (MSn) using triple quadrupole and quadrupole ion trap mass spectrometers. Two discrete gas phase fragmentation pathways for the loss of water from glycine-containing peptides, corresponding to retro-Koch and retro-Ritter type reactions were observed. Two pathways were also observed for the loss of water from C-terminal cysteine-containing peptides: a retro-Koch type reaction and an intramolecular nucleophilic attack at the carbonyl of the amide bond by the cysteinyl side chain thiol. Various intermediates involved in these reactions, derived from the [M+H−H2O]+ ions of N-formylglycine and N-formylcysteine, were modeled using ab initio calculations at the MP2(FC)/6-31G*//HF/6-31G* level of theory. These calculations indicate that: (i) the retro-Koch reaction product is predicted to be more stable than the product from the retro-Ritter reaction for N-formylglycine, and (ii) the intramolecular nucleophilic attack product is preferred over the retro-Koch and retro-Ritter reaction products for N-formylcysteine. The results from these ab initio calculations are in good agreement with the experimentally determined ion abundances for these processes.

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Authors and Affiliations

  1. Joint Protein Structure Laboratory, The Ludwig Institute for Cancer Research and the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    Gavin E. Reid & Richard J. Simpson

  2. School of Chemistry, University of Melbourne, Parkville, Victoria, Australia

    Gavin E. Reid & Richard A. J. O’Hair

Authors
  1. Gavin E. Reid
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  2. Richard J. Simpson
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  3. Richard A. J. O’Hair
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Correspondence to Richard A. J. O’Hair.

Additional information

Dedicated to the memory of Professor B.S. Freiser, a true innovator in gas phase ion chemistry.

Gas Phase Ion Chemistry of Biomolecules, Part 10. For part 9 see [3].

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Reid, G.E., Simpson, R.J. & O’Hair, R.A.J. A mass spectrometric and ab initio study of the pathways for dehydration of simple glycine and cysteine-containing peptide [M+H]+ ions. J Am Soc Mass Spectrom 9, 945–956 (1998). https://doi.org/10.1016/S1044-0305(98)00068-3

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  • DOI: https://doi.org/10.1016/S1044-0305(98)00068-3

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