Rapid, Stable, Chemoselective Labeling of Thiols with Julia–Kocieński-like Reagents: A Serum-Stable Alternative to Maleimide-Based Protein Conjugation

Authors

  • Dr. Narihiro Toda,

    1. The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
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    • These authors contributed equally to this work.

  • Dr. Shigehiro Asano,

    1. The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
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    • These authors contributed equally to this work.

  • Prof. Dr. Carlos F. Barbas III

    Corresponding author
    1. The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
    • The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)

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  • This study was supported by National Institutes of Health Pioneer Award DP1 CA174426.

Abstract

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Exquisite chemoselectivity for cysteine has been found for methylsulfonylphenyloxadiazole compounds under various buffer conditions. Furthermore, the resulting protein conjugates have superior stability to cysteine–maleimide conjugates in human plasma (HSA=human serum albumin, MBP-C-HA=maltose-binding protein). This new thiol-click reaction offers a new approach to generate stable protein conjugates and Pegylated proteins.

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