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The role of sulfur and sulfur isotope dilution analysis in quantitative protein analysis

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Abstract

The element sulfur is almost omnipresent in all natural proteomes and plays a key role in protein quantification. Incorporated in the amino acids cysteine and methionine, it has been served as target for many protein-labeling reactions in classic quantitative proteomic approaches based on electrospray or MALDI mass spectrometry. This critical review discusses the potential and limitations of sulfur isotope dilution analysis (IDA) by inductively coupled plasma—mass spectrometry (ICP-MS) for absolute protein quantification. The development of this approach was made possible due to the improved sensitivity and accuracy of sulfur isotope ratio measurement by ICP-MS in recent years. The unique feature of ICP-MS, compound-independent ionization, enables compound (species)-unspecific sulfur IDA. This has the main advantage that only one generic sulfur standard (i.e., one isotopically labeled sulfur spike) is required to quantify each peptide or protein in a sample provided that they are completely separated in chromatography or electrophoresis and that their identities are known. The principles of this approach are illustrated with selected examples from the literature. The discussion includes also related fields of P/S and metal/S ratio measurements for the determination of phosphorylation degrees of proteins and stoichiometries in metalloproteins, respectively. Emerging new areas and future trends such as protein derivatization with metal tags for improved sensitivity of protein detection in ICP-MS are discussed.

The key role of sulfur in protein quantification

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Acknowledgements

This work has been supported by a Marie Curie Intra-European Fellowship for Dr. Christina Rappel of the European Community program FP6-2005-Mobility-5 under contract number MEIF-CT-2006–041246.

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  1. Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, CNRS UMR 5254, Hélioparc, 2, avenue du Président Angot, F-64053, Pau, France

    Christina Rappel & Dirk Schaumlöffel

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  1. Christina Rappel
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  2. Dirk Schaumlöffel
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Correspondence to Dirk Schaumlöffel.

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Rappel, C., Schaumlöffel, D. The role of sulfur and sulfur isotope dilution analysis in quantitative protein analysis. Anal Bioanal Chem 390, 605–615 (2008). https://doi.org/10.1007/s00216-007-1607-2

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