Uses of Peptide Drugs
Peptides are bioactive substances involved in various cellular functions within organisms. Since biochemists synthesized peptides artificially over 40 years ago, the rapid development of molecular biology and biochemistry technologies has led to remarkable and epoch-making progress in peptide research. It has been discovered that there are tens of thousands of peptides in organisms, and all cells can synthesize peptides. Almost all cells are regulated by peptides, involving hormones, nerves, cell growth, and reproduction. In the foreseeable future, human research and application of peptides will enter a glorious period, making this century a world of peptides. Currently, the application of peptides mainly focuses on peptide drugs, peptide drug carriers, tissue engineering materials, and peptide nutritional foods.
1.Anti-tumor Peptides: The occurrence of tumors is the result of various factors, ultimately involving the regulation of oncogene expression. Different tumors require different regulatory factors such as enzymes during their formation. By selecting specific small peptides to act on the regulatory factors needed for tumor formation and blocking their active sites, tumor occurrence can be prevented. Many tumor-related genes and regulatory factors have been discovered, and screening peptides that specifically bind to these targets has become a new hotspot in the search for anti-cancer drugs. For example, American researchers discovered a small peptide (6 amino acids) that can significantly inhibit the growth of adenocarcinoma in the body, including lung, stomach, and colon adenocarcinoma, opening a new path for treating these highly fatal malignant tumors. Swiss scientists discovered another small peptide (8 amino acids) that can enter tumor cells, activate the anti-cancer gene P53, and induce apoptosis of tumor cells.
2.Antiviral Peptides: Viral infections generally go through multiple stages, including adsorption (host cells), penetration, uncoating, nucleic acid replication, transcription and translation, and packaging. Blocking any of these processes can prevent viral replication. The most effective antiviral drugs should act on the stages of viral adsorption and nucleic acid replication. Therefore, screening for antiviral drugs mainly focuses on these two stages. Viruses adsorb to cells by binding to specific receptors on host cells and rely on their own specific proteases for protein processing and nucleic acid replication. Thus, peptides that bind to host cell receptors or viral protease active sites can be screened from peptide libraries for antiviral treatment, which will become the largest market for replacing antibiotic drugs.
3.Peptide-Directed Drugs: Many toxins (such as Pseudomonas aeruginosa exotoxin) and cytokines (such as the interleukin series) have strong tumor cell toxicity but can also damage normal cells when used long-term or in large quantities. By fusing peptides that specifically bind to tumor cells with these active factors, these active factors can be specifically concentrated in the tumor area, greatly reducing the usage concentration and side effects of toxins and cytokines. For example, many tumor cells have epidermal growth factor receptors on their surface, which are tens to hundreds of times more numerous than on normal cells. By fusing toxins or anti-tumor cytokines with epidermal growth factor, these active factors can be specifically concentrated in tumor cells. Several companies have successfully expressed the fusion of epidermal growth factor and Pseudomonas aeruginosa exotoxin. Similarly, small peptides that specifically bind to tumor antigens screened from peptide libraries can also be used for directed drugs. Due to their small molecular weight, they are more suitable for directed drugs than murine monoclonal antibodies.
4.Cytokine Mimetic Peptides: Utilizing known cytokine receptors to screen cytokine mimetic peptides from peptide libraries has become a research hotspot in recent years. Internationally, mimetic peptides for human erythropoietin, human thrombopoietin, human growth hormone, human nerve growth factor, and interleukin-1 have been screened. These mimetic peptides have different Amino Acid sequences from their corresponding cytokines but possess cytokine activity and have the advantage of a smaller molecular weight. These cytokine mimetic peptides are currently in preclinical or clinical research stages.
5.Antimicrobial Active Peptides: When insects are stimulated by external environmental factors, they produce a large number of cationic peptides with antimicrobial activity. Over a hundred antimicrobial peptides have been screened, and in vitro and in vivo experiments have confirmed that several antimicrobial peptides not only have strong bactericidal capabilities but can also kill tumor cells. For example, the antimicrobial peptide D screened from silkworms shows great application prospects and can be produced using genetic engineering technology. Snake venom also contains various active peptides. A small peptide with 13 amino acids (INKAIAALAKKLL) isolated from snake venom has strong bactericidal capabilities against both G+ and G- bacteria.
6.Peptides for Cardiovascular Diseases: Many traditional Chinese medicines have effects such as lowering blood pressure, reducing cholesterol, and preventing thrombosis. They can be used not only as medicines but also as health foods. However, the active ingredients in these medicines are often not well-defined, limiting their use. Many effective components have been identified as small peptides. For example, Chinese scientists have processed and isolated active peptides from soybeans that can be directly absorbed through the small intestine, preventing thrombosis, hypertension, and hyperlipidemia, as well as delaying aging and enhancing the body’s tumor resistance. Small peptides for cardiovascular diseases have also been isolated from plants such as ginseng, tea leaves, and ginkgo leaves.
7.Other Medicinal Peptides: In addition to the significant progress made in the above areas, small peptide drugs have also achieved some advancements in other fields. For example, Steinberg et al. discovered a synthetic peptide (TP508) that can promote the regeneration of blood vessels in wounds and accelerate the healing of deep skin wounds. Pfister et al. found a small peptide (RTR)4 that can prevent the infiltration of inflammatory cells into the cornea after alkali damage and inhibit inflammatory responses. Carron et al. confirmed that two synthetic peptides they screened can inhibit osteoclast resorption of bone.
8.Diagnostic Peptides: The primary use of peptides in diagnostic reagents is as antigens to detect antibodies against viruses, cells, mycoplasma, spirochetes, and other microorganisms, as well as parasites such as cysticercus and trypanosomes. Peptide antigens have stronger specificity than natural microbial or parasite protein antigens and are easier to prepare. Therefore, diagnostic reagents assembled with peptide antigens have low false-negative rates and background reactions, making them suitable for clinical application. Currently, antibody detection reagents assembled with peptide antigens include those for hepatitis A, B, C, and G viruses, HIV, human cytomegalovirus, herpes simplex virus, rubella virus, syphilis spirochetes, cysticercus, trypanosomes, Lyme disease, and rheumatoid arthritis. Most of the peptide antigens used are screened from the natural proteins of the corresponding pathogens, while some are newly selected small peptides from peptide libraries.
9.Peptide Vaccines: Like nucleic acid vaccines, peptide vaccines are currently one of the most important research areas in vaccine development. Extensive research has been conducted on viral peptide vaccines. Currently, there are no ideal vaccines for two major viral diseases that pose significant threats to humans: AIDS and hepatitis C. The research results of nucleic acid vaccines and peptide vaccines are encouraging. In 1999, the NIH in the United States announced two HIV-1 peptide vaccines. Clinical trials on humans showed that these two peptides could stimulate the body to produce specific antibodies and specific cellular immunity with good safety. Tsinghua University in China also confirmed that a segment of a peptide in the HIV-I membrane protein has strong immunogenicity. Hepatitis C virus peptide vaccines also show promising development prospects. Foreign researchers have screened a peptide from the outer membrane protein E2 of the hepatitis C virus (HCV) that can stimulate the body to produce protective antibodies. Research on peptide vaccines for other viruses (such as hepatitis A, measles, Sindbis virus, etc.), as well as anti-tumor and contraceptive peptide vaccines, has also made significant progress. For example, American scholar NaZ and
Others screened a 12-amino acid peptide from a phage peptide library that can specifically bind to human eggs, preventing the binding of sperm and eggs, which can be used for contraceptive vaccines.
10.Peptide Drug Carriers: Peptides can be used as drug carriers, either as modifiers of drug carriers or as the main components of drug carriers. For example, [aw and others designed peptide segments connected by protease cleavage points that self-assemble in suitable solvents to encapsulate drugs in microspheres. When encountering target proteases, the cleavage points break, achieving targeted drug release. Peng Shiqi and others modified liposomes with the tetrapeptide arginine-glycine-aspartic acid-serine (Arg-Gly-Asp-Ser, RGDS) to use as drug carriers for targeted thrombolysis. Using the fibrinogen (FG) receptor ligand RGDS peptide of platelets as a homing device, they coupled it to the liposome carrier encapsulating urokinase (UK) with an acid-sensitive covalent bond. This can biodegrade into endogenous substances like Glu in nature or the human body, reducing accumulation and toxic side effects.
11.Tissue Engineering Materials: Some non-bioactive high molecular weight peptides, such as polyaspartic acid, polylysine, and polyglutamic acid, have advantages such as good biocompatibility, controllable biodegradation rate, modifiability, design plasticity, and structural controllability. These have gradually become a new type of material with great application prospects in tissue engineering. Langer and others prepared poly(lactic acid-lysine) and grafted RGD peptides onto the -NH2 of lysine in the polymer, effectively improving the cell adhesion ability of the polymer surface. This overcomes the lack of active groups in the main chain, resulting in tissue engineering scaffold materials that facilitate cell recognition and support cell growth.
12.Peptide Nutritional Foods: Active peptide foods, as a new type of health food or food additive, have unique characteristics and functions. They also have many advantages in nutrition and have broad application prospects in the food industry.
