Application of Peptides in Pharmaceutical Industry

Introduction

Peptides, the highly adjustable molecules, are receiving increasing attention in pharmaceutical industry for their maximum possibilities of being customized to achieve ideal biocompatibility and biodegradability, as well as selective and effective therapeutic effects. In addition to the characteristic high target affinity, peptides exhibit noteworthy stability beyond expectations. At present, the application of peptides in the pharmaceutical industry is mainly concentrated on peptide drugs, peptide drug carriers, etc.

1 Antiviral peptides

Virus infection generally undergoes multiple stages such as adsorption (to host cell), penetration, uncoating, nucleic acid replication, transcription and translation, and packaging. The screening of antiviral drugs largely focuses on the two stages of virus adsorption and nucleic acid replication. Viruses bind to specific receptors on host cells for adsorption and rely on their own specific proteases for protein processing and nucleic acid replication. Therefore, polypeptides binding to host cell receptors or active sites such as viral proteases can be screened from peptide libraries for use in antiviral therapy. Recent findings suggested that HCV nonstructural protein 3 (NS3) is a protease closely related to virus replication, and its active site has been determined. Moreover, Canada, Italy, and other countries have screened from the peptide library to confirm that a 6 peptide (DDIVPC) can significantly inhibit the enzyme activity.

2 Anti-tumor peptides

Multiple factors may result in the occurrence of tumors, but ultimately all involve the regulation of oncogene expression. Different tumors are caused by disparate enzymes or regulatory factors. Therefore, selecting specific small peptides as regulatory factors required for tumorigenesis and blocking the active site can contribute to the prevention of tumorigenesis. Many tumor-related genes and regulatory factors have been discovered, and the screening of peptides that specifically bind to these targets has emerged to be a new hot spot in the search for anti-cancer drugs. American scholars have discovered a small peptide (6 amino acids) to remarkably inhibit the growth of adenocarcinomas, including lung, stomach, and large intestine adenocarcinoma, opening up an opportunity for the treatment of malignant tumors with high mortality. Meanwhile, Swiss scientists have found another small peptide (8 amino acids), which can enter tumor cells, activate the anti-oncogene P53, and induce tumor cell apoptosis.

3 Cytokine mimic peptides

The use of known cytokine receptors to screen cytokine mimic peptides from peptide libraries has drawn considerable attention in recent years. Human erythropoietin, human thrombopoietin, human growth hormone, human nerve growth factor, and interleukin-1 have been screened to mimic peptides of multiple growth factors. The amino acid sequence of these mimetic peptides is different from that of the corresponding cytokine. However, the activity of cytokine and the advantage of small molecular weight are embodied in these cytokine mimetic peptides that are now in the preclinical or clinical research stage.

4 Antimicrobial peptides

When insects are stimulated by the external environment, they will produce a large number of cationic polypeptides with antibacterial activity. More than one hundred kinds of antimicrobial peptides have been screened out. In vivo and in vitro experiments have confirmed that multiple antimicrobial peptides not only have strong bactericidal ability but also can kill tumor cells. For example, the antimicrobial peptide D screened from silkworms has shown promising application prospects and can be produced by genetic engineering technology. There are many active peptides in snake venom as well. A small peptide with 13 amino groups (INKAIAALAKKLL) is isolated from snake venom, which has strong bactericidal ability against G+ and G- bacteria.

5 Diagnostic peptides

Polypeptides are used as antigens in diagnostic reagents to detect antibodies against viruses, cells, mycoplasma, spirochetes, other microorganisms, and parasites such as cysticercosis and trypanosoma. Polypeptide antigens are more specific than natural microorganisms or parasite protein antigens and are easily prepared. Therefore, the assembled detection reagents have a low false negative rate for detecting antibodies and high availability in clinical application. Antibody detection reagents assembled with peptide antigens can detect A, B, C, G or hepatic virus, AIDS virus, human cytomegalovirus, herpes simplex virus, rubella virus, and so on. Most of the peptide antigens are obtained from the natural protein analysis and screening of the corresponding pathogens while some are new small peptides screened from the peptide library.

6 Peptides for cardiovascular disease

Many plant-derived drugs have the effects of lowering blood pressure and blood lipids, as well as dissolving thrombosis. They can be used not only as medicines but also as health foods. A lot of active ingredients are found in small molecular peptides, such as active peptides processed and isolated from soybeans, which can be directly absorbed through the small intestine and can prevent thrombosis, high blood pressure, and hyperlipidemia. However, the peptides' application is restricted to a large extent due to the uncertainty of the active ingredients.

7 Peptide vaccine

Like nucleic acid vaccines, peptide vaccines are currently one of the important directions in the field of vaccine research. At present, a lot of research has been done on peptide vaccines for the two viral diseases, AIDS and hepatitis C, which are extremely harmful to humans. Fortunately, encouraging achievements have been made during the last decades. In 1999, the US NIH announced the results of phase I clinical trials of two HIV-I virus peptide vaccines in humans, confirming that these two peptides can stimulate the body to produce specific antibodies and cellular immunity with adequate safety. Some scholars have screened out general peptides from the outer membrane protein E2 of hepatitis C virus (HCV), which can stimulate the production of protective antibodies. Research on polypeptide vaccines for other viruses (such as hepatitis A, measles, Sindbis virus, etc.), anti-tumor vaccines, and contraceptive vaccines has also seen great progress. For example, the American scholar NaZ et al. screened a small 12-amino acid peptide from the phage peptide library for contraceptive vaccines, which can specifically bind to egg cells and prevent the binding of sperm and eggs.

8 Peptide drug carrier

Polypeptides can be used as modifiers or the main components of drug carriers. Researchers design a peptide segment connected to the breakpoint of the protease, which is self-assembled in a suitable solvent to coat the drug in the microsphere. When it encounters the targeted protease, the breakpoint is broken to achieve the targeted release of the drug. Arg-Gly-Asp-Ser (RGDS) tetrapeptide-modified liposomes are used as drug carriers to guide thrombolysis. The carrier and the drug are connected in the form of an acid-sensitive covalent bond, which can be biodegraded into the endogenous substance Glu in nature or the human body, and the accumulation and toxic side effects are rarely produced.

Conclusion

The huge clinical potential of peptide products is reflected in the fact that there are more than 60 peptide-based therapies on the market and another 500 derivatives currently in the development stage. The versatility and tunability of peptide-based products have led to an increase in the translation of peptide therapy. However, there are still major challenges in its implementation requiring further technological advances.