Synthesis of Proteins by Native Chemical Ligation
- 4 November 1994
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 266 (5186), 776-779
- https://doi.org/10.1126/science.7973629
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.Keywords
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