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Convergent Chemical Synthesis of [Lysine24, 38, 83] Human Erythropoietin†

Authors

  • Dr. Suhuai Liu,

    1. Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, The University of Chicago, 929 East 57th Street, Chicago, IL 60637 (USA)
    2. Institute for Biophysical Dynamics, Gordon Center for Integrative Science, The University of Chicago (USA)
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  • Dr. Brad L. Pentelute,

    1. Department of Chemistry, Gordon Center for Integrative Science, The University of Chicago (USA)
    2. Institute for Biophysical Dynamics, Gordon Center for Integrative Science, The University of Chicago (USA)
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  • Prof. Dr. Stephen B. H. Kent

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, The University of Chicago, 929 East 57th Street, Chicago, IL 60637 (USA)
    2. Department of Chemistry, Gordon Center for Integrative Science, The University of Chicago (USA)
    3. Institute for Biophysical Dynamics, Gordon Center for Integrative Science, The University of Chicago (USA)
    • Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, The University of Chicago, 929 East 57th Street, Chicago, IL 60637 (USA)
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  • †

    This research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02 07ER64501 to S.B.H.K. and by the National Institutes of Health, Grant No. R01 GM075993 to S.B.H.K.

Abstract

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A new route to EPO: Nonglycosylated human erythropoietin (EPO) was prepared using a convergent chemical ligation synthetic strategy. The synthetic [Lysine24, 38, 83] EPO analogue, which was purified by HPLC and has the correct molecular weight (see picture), shows well-defined covalent structure, is correctly folded, and is biologically active in a factor-dependent cell line assay.

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Article Information

DOI

10.1002/anie.201106060

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Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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Keywords

  • erythropoietin;
  • kinetically controlled ligation;
  • native chemical ligation;
  • proteins;
  • solid-phase synthesis

Publication History

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  • Version of record online:
  • Manuscript Revised:
  • Manuscript Received:

Funded by

  • Office of Science (BER), U.S. Department of Energy. Grant Number: DE-FG02 07ER64501
  • National Institutes of Health. Grant Number: R01 GM075993

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