Protein synthesis by chemical ligation of unprotected peptides in aqueous solution

Tom W. Muir, Philip E. Dawson, Stephen B.H. Kent

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


In these studies we have shown that reaction of a peptide-α-thioacid with an aryl disulfide gives a product with mass consistent with a 1-acyl-2- aryl disulfide species as the initial product, but that this is rapidly converted in situ to give a peptide-α-thioester, which can be isolated for use in native chemical ligation. In addition, we have demonstrated that peptide α-thioesters can be readily interconverted using transthioesterification reactions, permitting the reactivity of peptide thioesters to be modulated with thiol-reducing agents during native chemical ligation. Finally, novel synthetic strategies have been developed that allow sequential and convergent native chemical ligations to be performed, allowing the assembly of protein analogs from multiple unprotected peptide building blocks. A wide range of protein systems has been accessed through total synthesis by native chemical ligation of unprotected peptides in aqueous solution.

Original languageEnglish (US)
Pages (from-to)266-298
Number of pages33
JournalMethods in enzymology
StatePublished - 1997

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology


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