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Free-Radical-Based, Specific Desulfurization of Cysteine: A Powerful Advance in the Synthesis of Polypeptides and Glycopolypeptides

Authors

  • Qian Wan Dr.,

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
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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 10065, USA, Fax: (+1) 212-772-8691
    2. Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, USA
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  • Support for this work was provided by the National Institutes of Health (CA28824). A postdoctoral fellowship (William H. Goodwin and Alice Goodwin and the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center, SKI) is gratefully acknowledged by Q.W. We thank Prof. Anderson R. Maxwell for providing helpful spectra, Dr. Jiehao Chen for helpful discussions, and Dr. George Sukenick, Sylvi Rusli, and Hui Fang 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 proofreading the manuscript.

Abstract

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Being specific: The specific conversion of Cys (seleno-Cys) into Ala by a free-radical-mediated reduction can be achieved in an aqueous medium under mild conditions (see scheme, PG=protecting group). The conversion can be achieved in the presence of all 20 natural amino acids as well as a range of functional groups. This native chemical ligation followed by the Cys into Ala conversion will enable the synthesis of complex peptides and glycopeptides.

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