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Issue 2, 2011
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On-line liquid chromatography neutral loss-triggered electron transfer dissociation mass spectrometry for the targeted analysis of citrullinated peptides

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Abstract

Citrullination is a post-translational modification of proteins which deiminates arginine, increasing the mass by 0.98 Da. Protein citrullination is a known biomarker for multiple sclerosis and a potential biomarker for rheumatoid arthritis. Collision-induced dissociation (CID) tandem mass spectrometry of citrullinated peptides produces a dominant neutral loss of isocyanic acid (HNCO, −43 Da) from the deiminated arginine amino acid side-chain. Here we show that the loss of isocyanic acid in CID can be used as a trigger for targeted analysis by supplemental activation electron transfer dissociation (saETD). Unlike CID, post-translational modifications (PTMs) are retained on peptide backbone fragments produced by saETD, improving the confidence in assignment of both peptide sequence and PTM site. The method is demonstrated for four synthetic peptides spiked into complex trypsin-digested saliva samples and a commercial six protein tryptic mixture. In contrast to CID alone, the neutral-loss triggered ETD approach results in high confidence identification of three of the four peptides, including an unexpected disulfide-bound dimer, and zero false positives.

Graphical abstract: On-line liquid chromatography neutral loss-triggered electron transfer dissociation mass spectrometry for the targeted analysis of citrullinated peptides

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Publication details

The article was received on 29 Jun 2010, accepted on 05 Nov 2010 and first published on 01 Dec 2010


Article type: Paper
DOI: 10.1039/C0AY00414F
Citation: Anal. Methods, 2011,3, 259-266
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    On-line liquid chromatography neutral loss-triggered electron transfer dissociation mass spectrometry for the targeted analysis of citrullinated peptides

    A. J. Creese, M. M. Grant, I. L. C. Chapple and H. J. Cooper, Anal. Methods, 2011, 3, 259
    DOI: 10.1039/C0AY00414F

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