Development of protein chemical synthesis using peptide thioester synthetic blocks

Emil Fischer was a pioneer in peptide chemistry, striving to elucidate the chemical nature of peptides and proteins. In 1901, he and his colleague published the first paper on the subject. Since then, peptide chemistry has advanced steadily to the point that it is now possible to synthesize polypeptides, including enzymes. In addition, chemical synthesis is flexible and not constrained by the limitations of protein biosynthetic systems. Thus, proteins with various modifications, including post-translational modifications, can be synthesized. Current protein synthesis uses peptide thioesters synthesized by solid-phase methods as building blocks. This review will explain why peptide thioesters are utilized as building blocks for polypeptide synthesis and discuss the evolution of thioester preparation methods, as well as their applications in protein synthesis.