Synthesis of proteins by native chemical ligation

Philip E. Dawson, Tom W. Muir, Ian Clark-Lewis, Stephen B.H. Kent

Research output: Contribution to journalArticlepeer-review

2829 Scopus citations

Abstract

A simple technique has been devised that allows the direct synthesis of native backbone proteins of moderate size. Chemoselective reaction of two unprotected peptide segments gives an initial thioester-linked species. Spontaneous rearrangement of this transients intermediate yields a full-length product with a native peptide bond at the ligation site. The utility of native chemical ligation was demonstrated by the one-step preparation of a cytokine containing multiple disulfides. The polypeptide ligation product was folded and oxidized to form the native disulfide-containing protein molecule. Native chemical ligation is an important step toward the general application of chemistry to proteins.

Original languageEnglish (US)
Pages (from-to)776-779
Number of pages4
JournalScience
Volume266
Issue number5186
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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