SYNTHESIS OF PROTEINS BY NATIVE CHEMICAL LIGATION

摘要

Proteins of moderate size having native peptide backbones are produced by amethod of native chemical ligation. Native chemicalligation employs a chemoselective reaction of two unprotected peptide segmentsto produce a transient thioester-linked intermediate. Thetransient thioester-linked intermediate then spontaneously undergoes arearrangement to provide the full length ligation product having anative peptide bond at the ligation site. Full length ligation products arechemically identical to proteins produced by cell free synthesis. Fulllength ligation products may be refolded and/or oxidized, as allowed, to formnative disulfide-containing protein molecules. The techniqueof native chemical ligation is employable for chemically synthesizing fulllength proteins.