SYNTHESIS OF PROTEINS BY NATIVE CHEMICAL LIGATION

A simple technique has been devised that allows the direct synthesis o f native backbone proteins of moderate size. Chemoselective reaction o f two unprotected peptide segments gives an initial thioester-linked s pecies. Spontaneous rearrangement of this transient intermediate yield s a full-length product with a native peptide bond at the ligation sit e. The utility of native chemical ligation was demonstrated by the one -step preparation of a cytokine containing multiple disulfides. The po lypeptide 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 .