Introduction
Peptides are compounds between small molecules and proteins. Peptides have a variety of structures, including chain polypeptides, cyclic peptides, etc., but because chain polypeptides are too flexible, they can be twisted and flipped at will, making them too loose to make medicines well. Researchers have introduced loop structures to restrict the activity of peptides, increase the stability of peptides, and make them exhibit better pharmacological activity and stability, thereby making it possible for more peptides to be made into drugs. With the maturity of peptide synthesis technology, biochemical and molecular biology technology, the research of therapeutic peptides has made epoch-making progress, and has become one of the important directions of research and development of pharmaceutical companies in various countries.

The development history of peptide drugs
Compared with traditional small-molecule drugs and large-molecule biological drugs (antibodies) that have been popular in recent years, peptide molecules have potential advantages in many aspects such as target selection, drug delivery methods, and production processes. Classic peptide drugs are made from human hormones, natural toxin peptides or antibiotics as the basic skeleton, and then modified by appropriate chemical modifications (including the use of unnatural amino acids, fatty acid side chain modifications, etc.). The main purpose of these modifications is to extend the half-life of polypeptide molecules, thereby reducing the frequency of administration and improving patient compliance. After years of development of these peptide molecules, their related R&D and production technologies have been very mature, and the market scale is also growing. Although not like the explosive growth of antibody drugs, and related technologies flourish, peptide drugs are basically blockbuster drugs, mainly used to treat chronic diseases. However, since traditional polypeptide molecules are mostly derived from human hormones or natural animal and plant extraction, the target is limited and the research and development efficiency is low. Therefore, new research and development platforms with ultra-high capacity synthetic peptide libraries and high-throughput screening technologies have begun to develop rapidly.

Currently, the screening methods for synthetic peptide libraries include OBOC (one-bead-one-compound) library screening, phage display, mRNA display, and SICLOPPS (split-intein circular ligation of peptides and proteins) methods. Among them, the phage display platform is represented by the technology platform of Bicycle Therapeutics. This technology originated from Sir Greg Winter's laboratory, combining phage display technology with a chemical reaction that promotes the cyclization of peptides to realize the display and amplification of cyclic peptides. Based on this platform, Bicycle has launched various cyclic peptide projects, including multivalent cyclic peptides, PDC and so on. The mRNA display platform is represented by PeptiDream's core technology platform RaPID. The core technology platform comes from the laboratory of Professor HiroakiSuga of the University of Tokyo. He combined the mRNA display technology with the introduction of unnatural amino acids to realize the mRNA display of cyclic peptide molecules carrying unnatural amino acids. At present, this new type of cyclic peptide drug has been marketed, that is, Apellis' C3 targeting molecule pegcetacoplan (trade name Empaveli).

The development direction of peptide drugs
According to the analysis of researchers, the future development direction of peptide drugs will focus on peptide immunity, the expansion of peptide functions, and the research of new peptide preparations.
1 Multifunctional peptide drugs
Multifunctional polypeptide drugs can be a single polypeptide for various indications, or a conjugate of multiple polypeptides, so as to perform multiple functions. For example, antibiotic peptides also have other biological functions, such as increasing the body's immunity and wound repair. The multifunctional peptide drugs that have been marketed include abiglutide, liraglutide and so on.
2 Cell penetrating peptides
Traditional peptide drugs are difficult to cross cell membranes due to their physical and chemical properties. The cell-penetrating peptide is a special kind of peptide, which can directly enter the cell through the cell membrane. For example, TAT is the first cell-penetrating peptide to be discovered. Its method of entering cells is efficient and has no toxic side effects on cells. Cell penetrating peptides can mediate small molecules, nucleic acids, polypeptides, and proteins into cells and increase their absorption.
3 Conjugation of peptides to other drugs
Polypeptides can be conjugated with small molecules, nucleotides, antibodies and other molecules, and the efficacy, safety, and targeting of the conjugate have been further improved. In the field of tumor therapy, more than 20 peptide-conjugated molecules have entered clinical trials.
4 Peptide vaccines
Traditional vaccines are divided into attenuated vaccines and inactivated vaccines. Polypeptide vaccines have the advantages of low price, high safety, and strong specificity. In addition, the peptide vaccine is artificially synthesized, and there is no phenomenon of virulence recovery or incomplete inactivation, and it is not easy to cause allergic reactions.
5 Antimicrobial peptide
As the problem of increased bacterial resistance becomes more and more serious, the development of traditional antibacterial drugs becomes more difficult. The clinical demand for new antibacterial drugs is particularly urgent. Unlike traditional antibacterial drugs, antimicrobial peptides act on the cell membrane of bacteria, resulting in increased permeability, thereby killing the bacteria.
6 Antiviral peptide
Antiviral peptide drugs mainly act on the stage of virus adsorption receptor and virus replication stage, and peptides that bind to cell surface receptors can be screened from the peptide library. These selected peptides have potential antiviral effects. The human immunodeficiency virus cell HIV is easy to mutate and has strong drug resistance. The peptide library is used to screen out the peptides against the envelope glycoprotein, which has a good anti-HIV effect. Some antiviral peptides have entered the clinical stage.

Conclusion
In the future, the form and concept of peptide drugs will continue to expand, and there will be profound changes and improvements in many aspects such as target coverage, mechanism of action, and drug delivery methods.