Peptides are viewed as the most versatile natural products that is endowed by nature. In general, peptides have a broad set of biotechnological applications ranging from antibiotics to personal hygiene. The most outstanding peptide categories are therapeutic peptides, cosmetic peptides, functional peptides and alike. Therapeutic peptides, as can be inferred from its name, have been derived in treatment of cancers through improvement of cellular uptake, drug targeting and vaccine development. Likewise, cosmetic peptides are famous for their anti-aging and beautifying effects. Functional peptides are a little bit different because they possess some extraordinary properties that will ensure efficacy, specificity, selectivity and low toxicity when used as therapeutic agents, which is really rare and precious.
What are the source of functional peptides?
A great number of peptides are from natural source and the majority of them have been used for chemoprevention and therapy of various cancers. They may be derived from marine products, food, venom components and other animal constituents. Of course, many peptides are synthesized and produced using chemical strategies. As well, those synthetic peptides are extensively studied in contemporary applications.
Antimicrobial Peptides, Cell Penetrating Peptides and MHC Peptides are three representative of functional peptides and next we’ll explore them one by one.
Antimicrobial peptides (AMPs), also called host defense peptides, are natural antibiotics produced by various organisms. In 1939, Dubos found the first AMP while extracting an antimicrobial agent from a soil bacillus strain. Up till now, approximately five thousand AMPs have been found or synthesized. Their common characteristics are: small peptide, heat-stable, strong cationic, no drug fastness.
Currently, AMPs have gained intensive attention in both pharmaceutical industry and research area as they have a wide spectrum of targets including viruses, bacteria, fungi, and parasites. AMPs work by targeting the lipopolysaccharide layer of cell membrane and some have rapid killing effect. They can kill in seconds after the initial contact with cell membrane. AMPs are also found to be capable of enhancing the activities of antibiotics through synergistic effects.
Cell Penetrating Peptides
To better treat cancer, tumor targeting is of essential importance, especially in the chemotherapeutic development. Therefore, pore-forming and cytotoxic peptides are used to enhance intracellular delivery and increase specific binding affinity to cancer cells. Yet, this approach met difficulties in targeting, penetration and localization within tumors. In order to overcome this very challenge, cell-penetrating peptides (CPPs) made their debut as a new class of tumor-targeting peptides that can greatly facilitate internalization of tumor markers and chemotherapeutic drugs.
Consisting of less than 40 amino acids, CPPs have strong cell penetrating capability. The application of CPPs for delivering biologically active molecules across cellular membranes into cells is considered as an important breakthrough in cell biology. Furthermore, newer classes of CPPs are being constantly introduced. Something interesting has been detected that certain cyclized CPPs have greater cellular uptake and binding selectivity when compared to their linear counterpart, especially when treating chemoresistant tumors.
CPPs could be mainly classified into five groups based on their Physical–chemical properties, which are cationic peptides, hydrophobic peptides, amphipathic peptides, proline-rich and antimicrobial peptides, and chimeric peptides.
MHC, major histocompatibility complex, is a set of cell surface proteins which are important for the acquired immune system to recognize foreign molecules. In 1936, Peter Gorer, a British immunologist, made the first descriptions on the MHC. As to the main function of MHC molecules, they can bind to antigens derived from pathogens and display them on the cell surface, which makes it easy for the appropriate T-cells to recognize them. Most importantly, MHC can interact with T cell receptor (TCR) and its co-receptors to optimize binding conditions for the TCR-antigen interaction. Traditionally, TCR has a low avidity and fast off-rate for MHC-peptides complexes. Via this way, antigen binding affinity and specificity, together with signal transduction effectiveness, can be greatly enhanced.
MHC peptide is also called MHC-Peptide Tetramer, which is a complex of four MHC molecules associated with a specific peptides and bounded to a fluorochrome. The development of the fluorescently labeled tetrameric MHC–peptide complex has enabled the direct visualization, quantification and phenotypic characterization of antigen-specific T cells by using flow cytometry, and has transformed scientists’ understanding of cellular immune responses.
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