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Native Chemical Ligation Combined with Desulfurization and Deselenization: A General Strategy for Chemical Protein Synthesis

Authors

  • Philip E. Dawson

    Corresponding author
    1. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Rd. La Jolla, CA 92037, USA tel:+1 858 784-7015 fax:+1 858 784-7319
    • Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Rd. La Jolla, CA 92037, USA tel:+1 858 784-7015 fax:+1 858 784-7319
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Abstract

Of the many approaches proposed to generalize the native chemical ligation approach for protein synthesis, the simple procedure of global desulfurization of peptide thiols has become the most widely adopted. In this review, the development of the native ligation–desulfurization strategy is described, focusing on the conversion of Cys to Ala following ligation at N-terminal Cys residues. Subsequent variations on this theme have broadened the scope to other natural amino acids including Phe, Leu, Val, and Lys, and even non-native peptide linkages such as isopeptide bonds on lysine side chains. Using insights from both selenocysteine–peptide side reactions and radical initiated desulfurization procedures, a new method for the selective deselenization of peptides containing both selenocysteine and cysteine residues has been developed. Together, these approaches represent a robust and flexible methodology for the synthesis of complex polypeptides without the use of protecting groups.

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