Isopeptide method: development of S-acyl isopeptide method for the synthesis of difficult sequence-containing peptides

Authors

  • Taku Yoshiya,

    1. Department of Medicinal Chemistry, Division of Medicinal Chemical Sciences, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan
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  • Nui Ito,

    1. Department of Medicinal Chemistry, Division of Medicinal Chemical Sciences, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan
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  • Tooru Kimura,

    1. Department of Medicinal Chemistry, Division of Medicinal Chemical Sciences, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan
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  • Yoshiaki Kiso

    Corresponding author
    1. Department of Medicinal Chemistry, Division of Medicinal Chemical Sciences, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan
    • Department of Medicinal Chemistry, Division of Medicinal Chemical Sciences, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan
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Abstract

A novel strategy for a more efficient synthesis of difficult sequence-containing peptides, the S-acyl isopeptide method, was developed and successfully applied. A model pentapeptide Ac–Val–Val–Cys–Val–Val–NH2 was synthesized via its water-soluble S-acyl isopeptide using an S-acyl isodipeptide unit, Boc–Cys(Fmoc–Val)–OH. An S-acyl isopeptide possessing excellent water solubility could be readily and quantitatively converted to the native peptide via an S[BOND]N intramolecular acyl migration reaction at pH 7.4. Thus, the S-acyl isopeptide method provides a useful tool in peptide chemistry. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.

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