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Alternative Fusion Protein Strategies to Express Recalcitrant QconCAT Proteins for Quantitative Proteomics of Human Drug Metabolizing Enzymes and Transporters

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Manchester Pharmacy School, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom
Faculty of Life Sciences, Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom
§ Gut Barrier Group, University of Manchester, Clinical Sciences Building, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, United Kingdom
Cite this: J. Proteome Res. 2013, 12, 12, 5934–5942
Publication Date (Web):October 14, 2013
https://doi.org/10.1021/pr400279u
Copyright © 2013 American Chemical Society

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    Abstract

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    QconCAT is a tool for quantitative proteomics, consisting of an artificial protein, expressed from an artificial gene, made up of a concatenated string of proteotypic peptides selected from the proteins under study. Isotopically labeled QconCAT (usually containing 13C6-arginine and 13C6-lysine) provides a standard for each proteotypic peptide included in its sequence. In practice, some QconCAT proteins fail to express at sufficient levels for the purpose of quantitative analysis. Two complementary methods are presented to express recalcitrant QconCAT proteins intended to quantify human hepatic enzymes and transporters.

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    Complete annotated sequences for all QconCAT proteins; tabulated Q peptides included in the QconCATs, indicating those successfully detected by triple–quadrupole mass spectrometry; and coverage of fusion QconCATs obtained by DDA experiments.

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