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      Synthesis of proteins by native chemical ligation.

      Science (New York, N.Y.)
      Amino Acid Sequence, Humans, Interleukin-8, chemical synthesis, chemistry, Molecular Sequence Data, Oxidation-Reduction, Protein Conformation, Protein Folding, Proteins

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          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 transient 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.

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