A One-Pot Three-Segment Ligation Strategy for Protein Chemical Synthesis


  • This work was supported by PICS 4862 (CNRS, CNRST), Institut Pasteur de Lille, Université Lille Nord de France, Cancéropôle Nord Ouest, Région Nord pas de Calais, and European Community.


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Three in one: Native chemical ligation (NCL) and bis(2-sulfanylethyl)amido (SEA) ligation allow the one-pot assembly of three peptide segments in the N-to-C direction. The SEA group (see picture, blue) is switched off by intramolecular disulfide bond formation during NCL. Then, a phosphine switches it on to trigger the second SEA ligation step. The K1 domain of the hepatocyte growth factor was synthesized and found to be biologically active.