Polypeptide drug is a kind of polypeptide biological drug which can be used in the prevention, treatment and diagnosis of diseases. Its preparation methods mainly include chemical polypeptide synthesis, separation and purification, and gene engineering, among which chemical polypeptide synthesis is the main preparation method of polypeptide drugs. Although polypeptide drugs can be obtained by isolation and purification from the organism, the natural polypeptide molecular content is small, which can not fully meet the needs of clinical application. The synthesis of chemical polypeptide is realized by the chemical reaction of amino acid condensation step by step. Generally, the process of adding amino acid one by one is repeated from the carboxyl end to the amino end.
Peptide drugs mainly include peptide vaccines, antitumor peptides, antiviral peptides, peptide guided drugs, cytokine mimic peptides, antibacterial active peptides, diagnostic peptides and other small medicinal peptides. Compared with the common organic small molecule drugs, polypeptide drugs have the outstanding characteristics of strong biological activity, small dosage, low side effects and significant curative effect. However, their half-life is generally short, unstable and easy to be rapidly degraded in vivo.
Compared with protein macromolecular drugs, peptide drugs, in addition to peptide vaccines, are relatively small in immunogenicity, low in dosage, higher in unit activity, easy to synthesize, modify and optimize, high in purity and controllable in quality, and can quickly determine the medicinal value.
Peptide vaccine is based on the known or predicted amino acid sequence of a certain antigen epitope in pathogen antigen gene, which is prepared by chemical peptide synthesis technology. Peptide vaccine is an important direction of vaccine research at present. It has been developed for the peptide vaccine of HIV and HCV. Traditional vaccines are generally prepared in two ways: one is attenuated vaccine that can induce immunity but does not cause disease, such as yellow fever, poliomyelitis and measles vaccine or BCG vaccine; the other is inactivated vaccine, such as pertussis, rabies virus and typhoid bacillus.
Because peptide vaccine is completely synthesized, there is no problem of virulence recovery or incomplete inactivation. In particular, some microbial pathogens can not get enough antigens through in vitro culture. Although some pathogens can be cultured in vitro, they have potential pathogenicity, immunopathology and other issues related to safety and effectiveness. Polypeptides, as immunogens that cause immune response of effector cells in vivo, will become a new type of vaccine.
Because of its targeting, safety and specificity, peptide drugs have attracted more and more attention in the development of anti-tumor drugs. Different peptide drugs have different mechanisms of action. It can inhibit the proliferation of tumor cells, promote the apoptosis of tumor cells to achieve direct anti-tumor effect, and also can enhance and stimulate the immune response of the body to tumor cells, inhibit tumor angiogenesis to achieve indirect anti-tumor effect. Moreover, the diversity and specificity of its mechanism of action can also achieve peptide transformation and fusion, and realize the highly effective, targeted and specific antitumor effect of peptides.
Peptide oriented drugs
The peptide with binding ability is fused with cytotoxin or cytokine, which is directed to the lesion to play a therapeutic role and reduce toxic and side effects. It is known that many toxins (such as exotoxin of Pseudomonas aeruginosa) and cytokines (such as interleukin Series) have strong cytotoxicity to tumor cells, but they can also damage normal cells in the long-term or large-scale use of human beings. By fusing polypeptides that can specifically bind to tumor cells with these active factors, these active factors can be specifically focused on the tumor site, which can greatly reduce the concentration of toxins and cytokines, and reduce their side effects.
Cytokine mimic peptide
It refers to the selection of peptides from peptide library that can specifically bind to cytokine receptor and have cytokine activity at the same time. The sequences of these mimic peptides are generally different from the amino acid sequences of cytokines. Cytokines that stimulate hematopoiesis, such as erythropoietin (EPO) and thrombopoietin (TPO), regulate the self-renewal, proliferation, differentiation, maturation and programmed death of hematopoietic cells through specific binding with their receptors. In recent years, phage display libraries and other technologies have been used to screen small molecules similar to cytokine activity, such as peptide and non peptide, which have been proved to have the biological function of stimulating hematopoiesis similar to cytokine in vitro and animal experiments. This laid a solid foundation for further exploring the mechanism of cytokine action and screening out ideal peptide / non peptide drugs simulating other cytokine functions.
5、 Antimicrobial active peptide
At present, hundreds of polypeptide molecules with antibacterial activity have been screened from insects and animals. Antimicrobial peptides have the characteristics of broad antibacterial spectrum, strong thermal stability, small molecular weight and small immunogenicity. The bactericidal mechanism of antimicrobial peptides is unique, and pathogens are not easy to produce drug resistance, which is expected to develop into a new generation of peptide antibiotics. However, some antimicrobial peptides have the characteristics of unstable spatial structure and hemolytic activity, which limit the clinical application. Therefore, the design or modification of natural antimicrobial peptides, the elimination of hemolytic activity based on the improvement of antibacterial activity, and the promotion of the application of antimicrobial peptides in medicine are expected to develop into new antibacterial drugs, which will provide a new way to solve the problem of increasing resistance of pathogens to traditional antibiotics.
The polypeptides screened from the pathogenic body or peptide library were used as diagnostic reagents to detect the presence of antibodies against pathogenic microorganisms and parasites. Including the detection of antibodies to hepatitis virus, HIV, rheumatoid disease, etc. The most important use of polypeptide in diagnostic reagents is to use it as an antigen to detect viruses, cells, mycoplasma, spirochetes and other microorganisms, as well as antibodies against cysticercosis, Trypanosoma and other parasites. Peptide antigen is more specific than natural microorganism or parasite protein antigen, and it is easy to prepare. Therefore, the false negative rate and background reaction of the assembled detection reagent are very low, so it is easy to clinical application.
At present, the peptide drugs extracted from animal tissues will be phased out gradually. The methods of chemical peptide synthesis and gene recombination will become complementary peptide drug production methods in a long time. At the time of rapid growth of chemical peptide synthesis drugs, the preparation of peptide drugs by gene recombinant expression has also attracted the attention of the industry. Compared with chemical peptide synthesis, gene recombination is more suitable for the preparation of long peptides, and with the progress of technology, the cost of producing peptide drugs by gene recombination is also constantly reduced.