What is a peptide?
A peptide is a naturally-occurring molecule consisting of two or more amino acids chemically bound to one another by peptide bonds. The covalent peptide bond is formed between the carboxyl (CO) group of the C-terminus of one amino acid and the amino (NH) group of the N-terminus of a second amino acid. The resulting amide bond (CO-NH) is characteristic of all peptides and proteins.
The word “peptide” is derived from the Greek word πεπτίδιο (peptidio) meaning “digested”. The incredible structural and functional diversity of peptides reflect the many indispensable roles of these molecules in human, animal and plant biology, notably as hormones in the regulation of target organ function; as antibodies in the mediation of immune responses to infection; and as pharmacological agents that modulate receptor activity. Nowadays, laboratory synthesis of bioactive peptides occurs on a large scale, and is one of the core operations at Genaxxon bioscience. Many synthetic peptides can be generated efficiently on a small or a large scale, with consistently high purity, bioactivity and stability. These features are highly sought-after in many chemical, biomedical and pharmacological applications, in which innovations in peptide chemistry are key in scientific, biomedical and pharmaceutical research.
How Are Peptides Formed?
In the living animal and plant cell, peptide and protein synthesis occurs at the ribosomes. In the laboratory, peptides are generated using liquid- or solid-phase peptide synthesis technologies. These two techniques make it possible to create a potentially vast number of peptides on a routine basis.
Read more about peptide synthesis >
The formation of an amide bond between two amino acids is a relatively straightforward process within the living cell. However, it can be a challenge to achieve this in vitro, using the chemistry known and applied today. There are two major requirements for success: firstly, the carboxyl (CO) terminus of the first amino acid must react with the amino (NH) terminus of the second amino acid. This is known as directed synthesis. For directed synthesis to succeed, neither amino acid should react with itself, nor should the positions of the two amino acids be swapped with each other. Secondly, as many amino acids possess additional chemical groups that are potentially capable of reacting with the carboxyl or the amino group of the amino acid, it is crucial to prevent these potential interactions from occurring. These prerequisites were first realised in 1901 when Emil Fischer, in collaboration with Ernest Fourneau, synthesized the first dipeptide, glycylglycine; and later, in 1951, when Vincent du Vigneaud synthesised Oxytocin, the first polypeptide to be produced in vitro.
Peptides are generally classified according to the number of amino acids contained within them. The shortest peptide possible, composed of just two amino acids, is termed a “dipeptide", a peptide with three amino acids is referred to as a “tripeptide", etc. “Oligopeptides” are peptides that contain between two and 20 amino acids. “Polypeptides” are typically composed of between 20 and 50 amino. Proteins consist of multiple polypeptides, and contain greater than 50 amino acids.
While Peptides are usually distinguished from proteins on the basis of their amino acid count, exceptions do exist: for example, certain longer peptides have been classified as proteins (e.g. amyloid beta), and in some instances, certain smaller proteins are referred to as peptides (e.g. insulin).
For more information about the similarities and differences among peptides and proteins, please read our Peptides vs. Proteins page >.
Classification of Peptides
Peptides are generally divided into several classes. These classes vary, depending on how the peptides themselves are naturally produced. For example, ribosomal peptides are produced from the translation of mRNA on the ribosomes. Ribosomal peptides include hormones and signaling molecules (e.g. tachykinin, vasoactive intestinal, opioid, pancreatic and calcitonin peptides) and antibacterial peptides (Microcins, produced by Gram-negative bacteria). Ribosomal peptides often go through a process of maturation by subsequent proteolysis of the pre-mature form into a smaller biological active peptide.
Non-ribosomal peptides (NRPs) are oligopeptides or smaller polypeptides that are synthesized independently of an RNA template by peptide-specific peptide synthetases. Most of the NRPs are synthesized step-by-step through multi-enzyme complexes that are specific to the respective peptide.
NRP synthesis often uses atypical amino acids or other substrates as building blocks (e.g. D-amino acids, β-amino acids, modified amino acids, or fatty acids). NRPs are frequently cyclic rather than linear, but branching, bridging, heterocyclic and polycyclic peptides are also not uncommon. NRPs possess different functions, e.g. as antibiotics (polymyxin, vancomycin), pigments (indigoidin), siderophores and toxins (microcystin, nodularin, cyanotoxin). NRPs frequently appear in plants, fungi, and single-celled organisms. Glutathione, for example, is a key mediator of antioxidant defences in aerobic organisms.
MHC class I peptides
Immunogenic peptides, produced in large numbers and diversity by the proteasome, are continuously synthesized in the cytoplasm, and constitute fission products of recycled antigens. The immune system continually monitors the body for the presence of viral infections and degenerate cells by checking whether cells have endogenous or foreign proteins present and for the presence of MHC-I protein complexes.
Milk peptides and peptones
Peptides are also produced by the enzymatic digestion of proteins (e.g. by lactobacilli during milk fermentation, whereby proteases digest milk proteins). Peptones are partially-hydrolysed proteins that are derived from animal milk or meat. Peptones are often used in the laboratory as a culture medium for cultivating fungi and bacteria.
A peptide mimetic is a small molecule that mimics the biological function of peptides, including hormones, cytokines, enzyme substrates and viruses. They typically arise either from modification of an existing peptide, or by the de novo synthesis of molecules that mimic peptides in structure, charge or mechanics. Irrespectively, the altered chemical structure is designed to advantageously adjust the molecular properties (e.g. improved stability or bioactivity). Such modifications involve changes to the peptide that would not otherwise occur naturally (e.g. altered backbones and the incorporation of atypical amino acids).
Peptidomimetics can be grouped into three different classes:
1. Modified peptides (exchange of one or a few amino acids, incorporation of D-amino form instead the naturally occurring L-form, or bridging of amino acids (all of them have a peptide-like scaffold);
2. Molecules that are structurally similar to the original peptide, but are composed of organic molecules other than amino acids; and
3. A chemical component that mimics the mechanistic action / effect of the original peptide.
A peptide fingerprint is a chromatographic pattern of a peptide. A peptide fingerprint is produced by partial fragmentation of the peptide, followed by two-dimensional (2-D) mapping of the resulting fragments.
A peptide library is composed of a large number of peptides that contain a systematic combination of amino acids. Peptide libraries are often utilized in the study of proteins for biochemical and pharmaceutical purposes. Solid-phase peptide synthesis is the most frequent peptide synthesis technique used to prepare peptide libraries.
Custom-made protein fragments and peptides, are synthesized in dedicated laboratories, such those at Genaxxon bioscience. The resulting products are most commonly used for protein-peptide interaction studies, ELISA assays, as inhibitors or for immunization purposes, e.g. HIV envelope peptides.