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Development of Efficient Methods for Accomplishing Cysteine-Free Peptide and Glycopeptide Coupling

Authors

  • Gong Chen Dr.,

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA, Fax: (+1) 212-772-8691
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  • Qian Wan Dr.,

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA, Fax: (+1) 212-772-8691
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  • Zhongping Tan Dr.,

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA, Fax: (+1) 212-772-8691
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  • Cindy Kan Dr.,

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA, Fax: (+1) 212-772-8691
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  • Zihao Hua Dr.,

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA, Fax: (+1) 212-772-8691
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  • Krishnakumar Ranganathan Dr.,

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA, Fax: (+1) 212-772-8691
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  • Samuel J. Danishefsky Prof.

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA, Fax: (+1) 212-772-8691
    2. Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, USA
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  • This work was supported by the NIH (CA28824 to S.J.D) and the New York State Breast Cancer Research and Education Fund (C020919).

Abstract

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As simple as A, B, C: Non-cysteine-based reiterative fragment coupling of glycopeptides involves a metal-free (TCEP) coupling of a peptidyl C-terminal phenolic ester containing an ortho-disulfide moiety (A) with an N-terminal glycopeptide whose C terminus is an alkyl thioester (B) to produce AB, whose N terminus contains an alkyl thioester. A AgCl-mediated coupling of AB with peptide C then produces the tridomainal peptide ABC. TCEP=tris(2-carboxyethyl)phosphine.

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