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However, the production of human insulin during the 20th century could not keep up with the high market demand, and animal-derived insulins, such as bovine and porcine insulin, dominated the insulin market for almost 90 years until they were replaced by recombinant insulin 5, 6. In 1923, insulin became the first commercial peptide drug and has since benefited thousands of diabetes patients to date. It was first isolated by Frederick Banting in 1921 and further developed by Frederick and Charles Best 3, 4, and was already available for patients with diabetes mellitus just a year after its first isolation. The discovery and development of insulin, a peptide with 51 amino acids, has been considered as one of the monumental scientific achievements in drug discovery. The first half of the 20th century witnessed the discovery of several life-saving bioactive peptides, such as insulin and adrenocorticotrophic hormone, which were initially studied and isolated from natural sources. The development of peptide drugs has thus become one of the hottest topics in pharmaceutical research. Since the synthesis of the first therapeutic peptide, insulin, in 1921, remarkable achievements have been made resulting in the approval of more than 80 peptide drugs worldwide. Research into therapeutic peptides started with fundamental studies of natural human hormones, including insulin, oxytocin, vasopressin, and gonadotropin-releasing hormone (GnRH), and their specific physiological activities in the human body 2.

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Therapeutic peptides are a unique class of pharmaceutical agents composed of a series of well-ordered amino acids, usually with molecular weights of 500-5000 Da 1.