To bring down the cost, convergent synthesis of proteins through the assembly of smaller polypeptides by chemical ligation has been achieved. In general, two peptide fragments are chemically bought together by reacting two latent reaction motifs located at the termini. Various methods for chemical protein ligation have been developed, although some suffer drawbacks when preparing polypeptides in opposite chirality (Table , Entries 1-4). Native chemical ligation (NCL) is commonly used whereby the thiol group of an N-terminal cysteine peptide and a C-terminal thioester of a reacting pair undergo trans-thioesterification, followed by an S-to-N acyl shift to yield a traceless native peptide bond (Figure ).