Polypeptides are a type of compound formed by connecting multiple amino acids through peptide bonds. They are usually composed of 10-100 amino acid molecules. They are connected in the same way as proteins and have a relative molecular mass of less than 10,000 Da.
In recent years, with the development and maturity of peptide synthesis technology, peptide drugs have become one of the hot spots in drug research and development. Due to their wide range of indications, high safety and significant efficacy, they have been widely used in tumors, cardiovascular and cerebrovascular diseases, and hepatitis. , diabetes, AIDS and other diseases, it has broad development prospects.
Reviewing the century-old development history of peptides
Since the peptide (insulin) was first used in the human body in 1922, a hundred years ago, technological progress has greatly promoted the development of peptide drugs.
1. Technological progress provides opportunities for the development of peptide drugs
- Restructuring technology (production aspects) in the 1980s
- Phage technology in the 1980s (discovery of active peptides)
- Chemical modification and cyclization technology in the 1990s (improving peptide bioavailability)
- After 2010, innovative peptide combination technologies (peptide conjugates, etc.)
- After 2020, protein crystal structure research (polypeptide action mechanism)
- After 2020, AI technology application (breakthrough in modular design method)
2. Peptide drugs are more widely used in clinical applications
The development of peptide drugs has also extended to many disease treatment fields, including anti-infection, anti-tumor, physiological regulation, pain, heart failure, osteoporosis, diabetes, vaccines, etc. It can be expected that peptide drugs will be used in some fields in the near future. The field may be superior to existing small molecule chemical drugs.
Several hot spots for future peptide development
01 Peptide Drug Conjugate
- From the Peptide Drug Conjugate technology, it will be expanded to coupling small molecules, proteins, RNA, antibodies, nuclides, etc.
- The clinical use of PDC currently under research around the world can almost cover tumors, tumor immunity, anti-infection, respiratory, rare diseases, etc., reflecting the clinical value of technological progress.
02 Research and development of active peptide ingredients
The research and development of active peptide ingredients can be used in combination drugs for tumor metastasis and tumor resistance, immunotherapy (neoantigenic peptides) and complement inhibitors, etc.
03 The exploration of peptides in the discovery of new compounds
- Based on the confirmation of protein crystal structures and the accumulation of AI algorithms, the hotspot residues in the binding site of target proteins are becoming more and more clear, and the binding sites of peptides based on clear amino acid compositions with target proteins will be wider (compared to antibodies), which is for discovery New therapeutic options offer opportunities without affecting the normal physiological functions of natural ligands.
- Peptides can also be called a step in the discovery of new small molecule compounds. For example, the chemical nature of Pfizer's anti-coronavirus drug Paxlovid is a peptide analogue. During the discovery process, the hotspot residues Met49, Met165, and His41 were obtained based on the AI algorithm. The lipid pocket and the final structural modification are hydrogen bonded with Gln189 and Glu166 to obtain chemical drugs that inhibit coronavirus protease 3CL.
Finally, many scholars have reported that the success rate of peptide drug development is higher than that of chemical molecular entities
At present, peptides, Peptide Drug Conjugate(PCD), and new innovative drug delivery system technologies are included in the key development areas of the national "14th Five-Year Plan" for the development of the pharmaceutical industry.
