Bio-reduction of Redox-Sensitive Albumin Conjugates in FcRn-Expressing Cells

Authors

  • Lorine Brülisauer,

    1. Swiss Federal Institute of Technology Zurich (ETHZ), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1–5/10, 8093 Zurich (Switzerland)
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  • Gina Valentino,

    1. Swiss Federal Institute of Technology Zurich (ETHZ), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1–5/10, 8093 Zurich (Switzerland)
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  • Sakura Morinaga,

    1. Swiss Federal Institute of Technology Zurich (ETHZ), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1–5/10, 8093 Zurich (Switzerland)
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  • Kübra Cam,

    1. Swiss Federal Institute of Technology Zurich (ETHZ), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1–5/10, 8093 Zurich (Switzerland)
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  • Dr. Jens Thostrup Bukrinski,

    1. Novozymes A/S, Krogshoejvej 36, 2880 Bagsvaerd (Denmark)
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  • Prof. Dr. Marc A. Gauthier,

    1. Institut National de la Recherche Scientifique (INRS), EMT Research Center, 1650 boul. Lionel-Boulet, Varennes, J3X 1S2 (Canada)
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  • Prof. Dr. Jean-Christophe Leroux

    Corresponding author
    1. Swiss Federal Institute of Technology Zurich (ETHZ), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1–5/10, 8093 Zurich (Switzerland)
    • Swiss Federal Institute of Technology Zurich (ETHZ), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Vladimir-Prelog-Weg 1–5/10, 8093 Zurich (Switzerland)===

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  • This work was financially supported by Novozymes A/S. L.B. gratefully acknowledges a doctoral fellowship from the Scholarship Fund of the Swiss Chemical Industry (SSCI) (2-70882-08). C. Wu (peptide disulfide synthesis), M. Detmar and F. Roudnicky (HUVEC cell line), A. Helenius (RFP-Rab7 plasmids), the Scientific Center for Optical and Electron Microscopy (ETHZ), and the Functional Genomics Center (UZH) are gratefully acknowledged for their experimental support.

Abstract

Disulfide-containing IgG-, Fc-, or albumin-based prodrugs that rely on FcRn-trafficking by endothelial cells for prolonged circulation in the body might be hampered by premature bio-reduction processes during FcRn-mediated recycling events. A detailed bio-reduction analysis of redox-sensitive albumin conjugates in two FcRn-expressing cell lines has been performed. The obtained results indicate that the FcRn-mediated recycling pathway is not (or is only poorly) bio-reducing.

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