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Native Chemical Ligation at Valine: A Contribution to Peptide and Glycopeptide Synthesis

Authors

  • Jin Chen Dr.,

    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
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  • Qian Wan Dr.,

    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
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  • Yu Yuan Dr.,

    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
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  • Jianglong Zhu Dr.,

    1. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
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  • Samuel J. Danishefsky Prof.

    1. Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027 (USA), Fax: (+1) 212-772-8691
    2. Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065 (USA)
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  • Support for this research was provided by the National Institutes of Health (CA28824). We thank Dr. George Sukenick, Hui Fang, and Sylvi Rusli of the Sloan-Kettering Institute's NMR core facility for mass spectral and NMR spectroscopic analysis (SKI core grant no.: CA02848). We would like to express our appreciation to Rebecca Wilson for her assistance in preparing the manuscript.

Abstract

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A Val-uable link: The title transformation is achieved by a two-step ligation, radical-based desulfurization strategy (see scheme; NCL=native chemical ligation). After S→N acyl transfer, in which the acyl acceptor is a γ-thiol valine derivative, and site-specific dethiolation, a valine residue appears at the site of ligation. This method accomplishes ligations at Thr-Val and Pro-Val sites, and allows successful ligation of glycopeptide fragments.

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