The primary structure of peptide drugs is composed of amino acids, which can be artificially designed first, and then obtained through synthesis and gene recombination technology. In addition, it can also be extracted from natural plants and animals to obtain new peptide components.

Discovery of natural active peptides

Extracting and isolating a single polypeptide molecule from living organisms in nature, and screening out active polypeptides with developmental value through a series of activity determination methods, is a new drug discovery model in the early stage of polypeptide drug research and development. In nature, many peptide molecules are involved in the body's metabolism, physiology or pathology. According to these naturally occurring phenomena, the pharmaceutical development value of peptides can also be discovered. For example, the listing of Exenatide and Liraglutide are good examples. Many peptide drugs have been successfully marketed as GMP peptide drugs for the treatment of diabetes. Carbetocin is also common peptide drug.

Peptide drug discovery based on peptide library

After chemical degradation or protease hydrolysis is used to degrade some natural proteins, a large number of polypeptide fragments will be produced, from which active polypeptides can be screened. In addition, the construction of a biosynthetic peptide library includes a phage peptide library, and a peptide library is displayed on the cell surface, from which lead polypeptide molecules can be screened. With the continuous maturity of synthesis technology, it is now easy to construct chemically synthesized peptide libraries and peptide drug screening. Such peptide libraries can be constructed by randomly synthesizing peptides of a certain length, with low cost and high speed.

Research and development of peptide drugs based on protein functional regions

When a protein performs its function, sometimes only a part of the functional region is required, not the entire sequence, and the drug effect can also be exerted by gene knockout or only the synthesis of peptide functional fragments, thereby avoiding the cumbersome process and high cost of genetic engineering to express proteins. , The disadvantage of difficult purification.

Research and development of peptide drugs based on molecular design and modification

The research and development of peptide drugs and the discovery of peptide lead compounds are still a costly and risky project. In recent years, computer-aided design based on various theoretical calculation methods and molecular simulation techniques has been used in the research and development of various peptide drugs. It is widely used. For example, the anti-AIDS drug Sifuvirtide is a human immunodeficiency virus (HIV) membrane fusion protein inhibitor, which is newly designed and synthesized based on the spatial structure of HIV membrane protein. Phase I and Phase II clinical trials show that Sifuvirtide has a good antiviral effect.