Peptide vaccine
Polypeptide vaccine, like nucleic acid vaccine, is one of the most important research areas in the field of vaccine research. In particular, a lot of research has been done on viral peptide vaccine.
At present, there is no ideal vaccine for HIV / AIDS and hepatitis C, which are the two most harmful viral diseases to human beings. The research results of nucleic acid vaccine and peptide vaccine are encouraging. In 1999, NIH published two kinds of HIV-I virus peptide vaccine.
The results of phase I clinical trial on human body confirmed that the two peptides can stimulate the body to produce specific antibodies and specific cellular immunity, and have good safety.
Tsinghua University in China has also confirmed that a polypeptide in HIV-I membrane protein has strong immunogenicity. Hepatitis C virus peptide vaccine also shows a good development prospect.
Foreign scholars have screened out the general peptide from the envelope protein E2 of hepatitis C virus (HCV), which can stimulate the body to produce protective antibodies. Great progress has also been made in peptide vaccines for other viruses (such as hepatitis A, measles, Sindbis virus, etc.) and peptide vaccines against tumors and contraception.
For example, American scholar Naz et al. Screened a 12 amino acid peptide from phage peptide library. It can specifically bind to human eggs and prevent sperm from binding to eggs, which can be used for contraceptive vaccine.
Antitumor polypeptide
Tumorigenesis is the result of many factors, but ultimately it involves the regulation of oncogene expression. Different tumors need different regulatory factors such as enzymes.
Selecting specific peptides as regulatory factors that are smaller than the ones needed for tumor occurrence, and blocking their active sites can prevent tumor occurrence. Now many tumor related genes and tumor producing regulatory factors have been found.
Screening peptides specifically binding to these targets has become a new hot spot in searching for anticancer drugs. A small peptide (6 amino acids) has been found in the United States, which can significantly inhibit the growth of adenocarcinoma in vivo, including lung, stomach and large intestine adenocarcinoma, which opens up a new way to treat this high mortality malignant tumor.
Swiss scientists have discovered another small peptide (8 amino acids), which can enter tumor cells, activate the anti-cancer gene p53, and induce tumor cell apoptosis.
Antiviral peptides
After virus infection, the virus usually goes through adsorption (host cell), penetration, shelling, nucleic acid replication, transcription, translation, packaging and other stages. Blocking either process prevents virus replication.
The most effective antiviral drugs should act on the two stages of virus adsorption and nucleic acid replication, so the screening of antiviral drugs mainly focuses on these two stages of virus replication. Virus adsorbs cells by binding to specific receptors on host cells, and relies on its own specific protease for protein processing and nucleic acid replication.
Therefore, peptides binding to host cell receptors or active sites such as viral proteases can be screened from the peptide library for antiviral therapy.
HCV nonstructural protein 3 (NS3) is a protease closely related to viral replication, and its active site has been identified. A 6-peptide (ddivpc) has been screened from peptide libraries in Canada, Italy and other countries, which can significantly inhibit the activity of NS3.
In addition, small peptides that can bind to retroviral enzyme necessary for HIV replication and peptides that can bind to HIV outer membrane protein to prevent virus from entering cells have been screened from peptide library. Some of these peptides have been put into clinical trials.
Peptide targeting drugs
It is known that many toxins (such as Pseudomonas aeruginosa exotoxins) and cytokines (such as interleukin Series) have strong tumor cytotoxicity, but they can also damage normal cells in long-term or large-scale use. If the peptides that can specifically bind to tumor cells are fused with these active factors, these active factors can be specifically concentrated in the tumor site, which can greatly reduce the concentration of toxins and cytokines, and reduce the side effects.
For example, there are epidermal growth factor receptors on the surface of many tumor cells, the number of which is dozens or even hundreds of times higher than that on normal cells. The fusion of toxin or anti-tumor cytokine with epidermal growth factor can specifically gather these active factors into tumor cells. Several domestic and foreign experts have successfully expressed epidermal growth factor with Pseudomonas aeruginosa exotoxin.
In addition, small peptides which can specifically bind to tumor antigen were screened from peptide library, and can also be used as targeting drugs. Because of their small molecular weight, they are more suitable for targeting drugs than mouse monoclonal antibodies.
Cytokine mimetic peptide
Screening cytokine mimetic peptides from peptide libraries by using known cytokine receptors has become a hot topic in recent years. Many kinds of growth factor mimetic peptides, such as human erythropoietin, human thrombopoietin, human growth hormone, human nerve growth factor and interleukin-1, have been screened abroad.
The amino acid sequences of these mimic peptides are different from those of their corresponding cytokines, but they have the activity of cytokines and have the advantages of small molecular weight. These cytokine mimetic peptides are in preclinical or clinical research stage.
Antibacterial active peptide
When insects are stimulated by the external environment, a large number of cationic peptides with antibacterial activity are produced. More than 100 kinds of antimicrobial peptides have been screened out.
Experiments in vivo and in vitro show that multiple antimicrobial peptides not only have strong bactericidal ability, but also kill tumor cells. For example, antimicrobial peptide D screened from silkworm showed good application prospects and could be produced by genetic engineering technology.
A 13 amino acid (inkaialakkll) peptide was isolated from snake venom, which had strong bactericidal activity against G + and G-bacteria.
Peptides for cardiovascular disease
Many herbal medicines have the effects of lowering blood pressure, blood lipid and hemolytic thrombus. They can be used not only as medicine, but also as health food. But because of its action, the composition is uncertain. Its application is limited.
It has been found that many effective ingredients are small molecular polypeptides. For example, the active polypeptides extracted from soybean by Chinese scientists can be directly absorbed through the small intestine, which can prevent and treat thrombosis, hypertension and hyperlipidemia, delay aging and improve the tumor power of the body. From ginseng, tea, ginkgo leaves and other plants, many small peptides used for cardiovascular disease were also isolated.
Other small medicinal peptides
In addition to the above-mentioned aspects, small peptide drugs have also made some progress in many other fields. For example, tiernberg found that a synthetic peptide (TP508) peptide can promote the regeneration of wound blood vessels and accelerate the healing of deep skin wounds.
Pfister et al. Found that a small peptide (RTR) 4 can prevent alkali injury of corneal inflammatory cells infiltration, inhibit inflammatory reaction. Carron et al. Confirmed that the two synthetic peptides could inhibit the resorption of bone by osteoclasts.
Diagnostic peptides
The most important use of peptides in diagnostic reagents is to detect antibodies against viruses, cells, mycoplasma, spirochetes and other microorganisms and parasites such as cysticercosis and Trypanosoma. Peptide antigens are more specific than natural microorganisms or parasite protein antigens, and are easy to prepare.
Therefore, the false negative rate and background reaction of the prepared detection reagents are very low, which is easy for clinical application Use.
At present, antibody detection reagents assembled with peptide antigens include: A, B, C, g or liver virus, HIV, human cytomegalovirus, herpes simplex virus, rubella virus, Treponema pallidum, cysticercosis, Trypanosoma, Lyme disease and rheumatoid. Most of the peptide antigens used are obtained from the natural proteins of the corresponding pathogens, and some of them are new peptides screened from the peptide library.
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