A more general approach to native (amide-forming) chemical ligation of unprotected peptide segments is described that extends the technique beyond the previously reported X-Cys ligation site to now include X-Gly and Gly-X ligation sites. A peptide,[peptide1] αCOSR, is reacted with a second peptide, HSCH2CH2 (O)-Nα [peptide2], under conditions promoting thioester exchange. The intermediate thioester-linked product rearranges to form a ...