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Science 4 November 1994:
Vol. 266. no. 5186, pp. 776 - 779
DOI: 10.1126/science.7973629
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Articles

Science, Vol 266, Issue 5186, 776-779
Copyright © 1994 by American Association for the Advancement of Science

articles

Synthesis of proteins by native chemical ligation

PE Dawson, TW Muir, I Clark-Lewis, and SB Kent

Scripps Research Institute, La Jolla, CA 92037.

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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