Chemical protein synthesis

Recombinant protein synthesis is limited, and with a few exceptions restricted to the exchange of the 21 proteinogenic amino acids. In contrast, chemical protein synthesis does not suffer from these limitations and is the prime method to access proteins with posttranslational modifications including, amongst others, phosphorylation, glycosylation and fatty acid modification. Solid phase peptide synthesis is the most powerful method for the synthesis of smallto medium-sized peptides (5-50 amino acids). To gain access to large peptides, the field relies on segment coupling enabled by the native chemical ligation (NCL, see Figure 1). This method involves the reaction between a C-terminal peptide thioester and an N-terminal cysteinyl peptide.