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Issue 1, 2017
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Serine promoted synthesis of peptide thioester-precursor on solid support for native chemical ligation

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Abstract

Fmoc solid phase peptide synthesis of thioesters for the chemical synthesis of proteins via native chemical ligation is a challenge. We have developed a versatile approach for direct synthesis of peptide thioesters from a solid support utilizing Fmoc chemistry. Peptide thioester synthesis is performed by the formation of a cyclic urethane moiety via a selective reaction of the backbone amide chain with the side group of serine. The activated cyclic urethane moiety undergoes displacement by a thiol to generate the thioester directly from the solid support. Importantly, the method activates the serine residue for the synthesis of peptide thioesters; thus it is fully automated and free of the types of resins, linkers, handles, and unnatural amino acids typically needed for the synthesis of peptide thioesters using Fmoc chemistry. The resulting thioester is free of epimerization and is successfully applied for the synthesis of longer peptides using NCL.

Graphical abstract: Serine promoted synthesis of peptide thioester-precursor on solid support for native chemical ligation

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Publication details

The article was received on 16 May 2016, accepted on 28 Jul 2016 and first published on 16 Aug 2016


Article type: Edge Article
DOI: 10.1039/C6SC02162J
Citation: Chem. Sci., 2017,8, 117-123
  • Open access: Creative Commons BY-NC license
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    Serine promoted synthesis of peptide thioester-precursor on solid support for native chemical ligation

    H. E. Elashal, Y. E. Sim and M. Raj, Chem. Sci., 2017, 8, 117
    DOI: 10.1039/C6SC02162J

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