Chemical synthesis of proteins

Proteins that contain non-natural amino acid residues (such as post- translationally modified proteins and proteins functionalized with synthetic probes) are highly important molecules in chemical biology. These molecules can't be readily obtained through biological expression, so that the only approach to produce them is to use chemical synthesis. Currently the most important method in the field of chemical synthesis of protein is cysteine-based native chemical ligation, which can efficiently condense peptide segments in aqueous solutions under mild conditions to generate natural as well as non-natural proteins. Here we systematically review the fundamental aspects of cysteine-based native chemical ligation. We also surveyed the recent progress in this field to improve the efficiency and scope of this particular ligation method. Finally, the representative applications of the ligation method in the synthesis of natural proteins, lipidated proteins, and glycoproteins are introduced.