Synthesis of proteins by native chemical ligation - PubMed (original) (raw)

. 1994 Nov 4;266(5186):776-9.

doi: 10.1126/science.7973629.

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Synthesis of proteins by native chemical ligation

P E Dawson et al. Science. 1994.

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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