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Probing the Frontiers of Glycoprotein Synthesis: The Fully Elaborated β-Subunit of the Human Follicle-Stimulating Hormone

Authors

  • Dr. Pavel Nagorny,

    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
    2. Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, NY 10027(USA)
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    • These authors contributed equally to this work.

  • Dr. Neeraj Sane,

    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
    2. Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, NY 10027(USA)
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    • These authors contributed equally to this work.

  • Dr. Bernhard Fasching,

    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
    2. Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, NY 10027(USA)
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  • Dr. Baptiste Aussedat,

    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
    2. Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, NY 10027(USA)
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  • Prof. Dr. Samuel J. Danishefsky

    Corresponding author
    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
    2. Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, NY 10027(USA)
    • Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
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  • This work was supported by NIH grant CA103823 (to S.J.D.) and NIH grant CA125934-02 (to P.N.). B.F. is grateful to the Austrian Fonds zur Förderung der wissenschaftlichen Forschung for a fellowship. We thank Rebecca Wilson for assistance with the preparation of the manuscript.

Abstract

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Ambitious undertaking: The β-subunit of the human follicle-stimulating hormone (hFSH) displaying a N-linked consensus sequence oligosaccharide at each of the two wild-type sites was synthesized. The glycoprotein has been designed with acetamidomethyl protected cysteine residues, anticipating folding and association with the α-subunit. This represents the largest realistically glycosylated homogeneous glycoprotein obtained by using strictly chemical methods.

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