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Neutral loss of water from the b ions with histidine at the C-terminus and formation of the c ions involving lysine side chains

Authors

  • Qiang Fu,

    1. Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, Wisconsin 53706, USA
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  • Lingjun Li

    Corresponding author
    1. Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, Wisconsin 53706, USA
    2. School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA
    • School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA.
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Abstract

Neutral loss of water from the amide bond induced by the His side chain has been reported. The proposed fragmentation pathway is a retro-Ritter reaction catalyzed by the imidazole nitrogen. In our MS/MS study of the neuropeptide GAHKNYLRFamide, we observed that the neutral loss of water from the b3 ion is abundant. The b3 ion has a His residue at the C-terminus. As reported previously, in the b ions with His at the C-terminus, the imidazole residue is connected to the carbonyl carbon to form a five-membered ring. Therefore, it is unlikely that the neutral loss of water from the b3 ion is catalyzed by the imidazole nitrogen. Through MS2 and MS3 studies of a synthetic peptide standard AGHKLL and its chemically labeled and isotope-encoded forms, we discovered that the water loss from the b3 ion involves the carbonyl group of His, the hydrogen connected to the α-carbon of Gly, and the amide hydrogen of His. We also discovered the formation of an unusual cx ion in peptides with a Lys or Arg residue at the (x + 1) position of the peptide. Copyright © 2006 John Wiley & Sons, Ltd.

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