Peptides exist widely in organisms, and tens of thousands of peptide drugs have been discovered so far. They participate in and regulate the functional activities of various systems, organs, tissues and cells in the body, and play an important role in life activities. Polypeptide drugs, as signaling molecules, regulate biological functions of organisms such as cell division, chemotaxis, pain, growth, immunity, etc., and as transport molecules, promote ions to pass through cell membrane channels. Today, peptide drugs have been used in many drug treatment fields, such as diabetes, cardiovascular and cerebrovascular diseases, obesity, tumors, arthritis, allergies, anti-infection, diagnosis, etc.
Since insulin was officially used in clinical practice 100 years ago, about 118 peptide drugs have been launched for the treatment of various diseases, continuing the century-old glory of the peptide industry.
In 1921, Dr. Frederick Banting and his assistant Charles Best discovered and successfully extracted insulin; in 1922, a 14-year-old type 1 diabetic patient received insulin injections and improved symptoms, which opened the first key milestone of polypeptide drugs. In 1923, Dr. Banting and physiologist John Macleod were awarded the Nobel Prize in Physiology or Medicine for their research on insulin.
In 1954, Vincent du Vigneaud's research team published "the total synthesis of oxytocin and vasopressin", and found that oxytocin is a peptide composed of nine amino acids, and successfully synthesized this hormone in vitro. It was chemically synthesized for the first time, and Vincent DiVigno was awarded the Nobel Prize in Chemistry in 1955.
In 1963, R. Bruce Merrifield invented the solid-phase peptide synthesis technology (Solid Phase Peptide Synthesis, SPPS). SPPS is an important milestone in peptide chemistry. Due to its convenient and rapid synthesis, it has become the preferred method for peptide synthesis, bringing a revolution in peptide organic synthesis and becoming an independent discipline. Merrifield won the 1984 Nobel Prize in Chemistry for this.
In 1958, the Shanghai Institute of Biochemistry of the Chinese Academy of Sciences was established. After 7 years of hard work, bovine insulin crystals were finally synthesized in 1965. This is the first time that humans have obtained protein/high molecular weight polypeptide drugs by means of chemical synthesis.
In 1978, the joint team of Genentech and the City of Hope National Medical Center announced the use of recombinant DNA technology to produce human insulin, the second-generation insulin, and obtained the cooperation of Eli Lilly. Through the efforts of Genentech and Eli Lilly, the recombinant human insulin drug was approved by the US FDA in October 1982, and large-scale production and sales of recombinant human insulin began.
The emergence of recombinant technology in the 1980s made it possible to produce peptide drugs with larger molecules, and then the strategy of increasing the molecular weight of peptide drugs by combining with lipids, macromolecular proteins, and polyethylene glycol was of great help in overcoming renal clearance and increasing plasma circulation. Issues such as timing helped. After 2000, natural peptides have been continuously enriched, especially the peptidomics from venom and new chemical modification methods are promoting the discovery of new peptide drugs. Especially in recent years, the emergence of emerging technologies such as multifunctional peptides, constrained peptides, conjugated peptides, oral peptides, long-acting, and delivery systems has greatly promoted the prosperity and development of the field of peptide drugs, and more cutting-edge "polypeptide new economic industry" has emerged.