What Are Peptides?

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What is a Peptide?

A peptide is a biologically occurring chemical compound containing two or more amino acids connected to one another by peptide bonds. A peptide bond is a covalent bond that is formed between two amino acids when a carboxyl group or C-terminus of one amino acid reacts with the amino group or N-terminus of another amino acid in a condensation reaction (a molecule of water is released during the reaction). The resulting bond is a CO-NH bond and forms a peptide, or amide molecule. Likewise, peptide bonds are amide bonds.

The word “peptide” itself comes from πέσσειν, the Greek word meaning “to digest.” Peptides are an essential part of nature and biochemistry, and thousands of peptides occur naturally in the human body and in animals. In addition, new peptides are being discovered and synthesized regularly in the laboratory as well. Indeed, this discovery and innovation in the study of peptides holds great promise for the future in the fields of health and pharmaceutical development.


How Are Peptides Formed?

Peptides are formed both naturally within the body and synthetically in the laboratory. The body manufactures some peptides organically, such as ribosomal and non-ribosomal peptides. In the laboratory, modern peptide synthesis processes can create a virtually boundless number of peptides using peptide synthesis techniques like liquid phase peptide synthesis or solid phase peptide synthesis. While liquid phase peptide synthesis has some advantages, solid phase peptide synthesis is the standard peptide synthesis process used today. Read more about peptide synthesis.

The first synthetic peptide was discovered in 1901 by Emil Fischer in collaboration with Ernest Fourneau. Oxytocin, the first polypeptide, was synthesized in 1953 by Vincent du Vigneaud.


Peptide Terminology

Peptides are generally classified according to the amount of amino acids contained within them. The shortest peptide, one composed of just two amino acids, is termed a “dipeptide.” Likewise, a peptide with 3 amino acids is referred to as a “tripeptide.” Oligopeptides refer to shorter peptides made up of relatively small numbers of amino acids, generally less than ten. Polypeptides, conversely, are typically composed of more than at least ten amino acids. Much larger peptides (those composed of more than 40-50 amino acids) are generally referred to as proteins.

While the number of amino acids contained is a main determinate when it comes to differentiating between peptides and proteins, exceptions are sometimes made. For example, certain longer peptides have been considered proteins (like amyloid beta), and certain smaller proteins are referred to as peptides in some cases (such as insulin). For more information about the similarities and differences among peptides and proteins, read our Peptides Vs. Proteins page.


Classification of Peptides

Peptides are generally divided into several classes. These classes vary with how the peptides themselves are produced. For example, ribosomal peptides are produced from the translation of mRNA. Ribosomal peptides often function as hormones and signaling molecules in organisms. These can include tachykinin peptides, vasoactive intestinal peptides, opioid peptides, pancreatic peptides, and calcitonin peptides. Antibiotics like microcins are ribosomal peptides produced by certain organisms. Ribosomal peptides often go through the process of proteolysis (the breakdown of proteins into smaller peptides or amino acids) to reach the mature form.

Conversely, nonribosomal peptides are produced by peptide-specific enzymes, not by the ribosome (as in ribosomal peptides). Nonribosomal peptides are frequently cyclic rather than linear, although linear nonribosomal peptides can often occur. Nonribosomal peptides can develop extremely intricate cyclic structures. Nonribosomal peptides frequently appear in plants, fungi, and one-celled organisms. Glutathione, a key part of antioxidant defenses in aerobic organisms, is the most common nonribosomal peptide.

Milk peptides in organisms are formed from milk proteins. They can be produced by enzymatic breakdown by digestive enzymes or by the proteinases formed by lactobacilli during the fermentation of milk. Additionally, peptones are peptides derived from animal milk or meat that have been digested by proteolytic digestion. Peptones are often used in the laboratory as nutrients for growing fungi and bacteria.

Peptide fragments, moreover, are most commonly found as the products of enzymatic degradation performed in the laboratory on a controlled sample. However, peptide fragments can also occur naturally as a result of degradation by natural effects.


Important Peptide Terms

There are some basic peptide-related terms that are key to a general understanding of peptides, peptide synthesis, and the use of peptides for research and experimentation:

Amino Acids – Peptides are composed of amino acids. An amino acid is any molecule that contains both amine and carboxyl functional groups. Alpha-amino acids are the building blocks from which peptides are constructed.

Cyclic Peptides – A cyclic peptide is a peptide in which the amino acid sequence forms a ring structure instead of a straight chain. Examples of cyclic peptides include melanotan-2 and PT-141 (Bremelanotide).

Peptide Sequence – The peptide sequence is simply the order in which amino acid residues are connected by peptide bonds in the peptide.

Peptide Bond – A peptide bond is a covalent bond that is formed between two amino acids when a carboxyl group of one amino acid reacts with the amino group of another amino acid. This reaction is a condensation reaction (a molecule of water is released during the reaction).

Peptide Mapping – Peptide mapping is a process that can be used to validate or discover the amino acid sequence of specific peptides or proteins. Peptide mapping methods can accomplish this by breaking up the peptide or protein with enzymes and examining the resulting pattern of their amino acid or nucleotide base sequences.

Peptide Mimetics – A peptide mimetic is a molecule that biologically mimics active ligands of hormones, cytokines, enzyme substrates, viruses or other bio-molecules. Peptide mimetics can be natural peptides, a synthetically modified peptide, or any other molecule that performs the aforementioned function.

Peptide Fingerprint – A peptide fingerprint is a chromatographic pattern of the peptide. A peptide fingerprint is produced by partially hydrolyzing the peptide, which breaks up the peptide into fragments, and then 2-D mapping those resulting fragments.

Peptide Library – 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

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What are Research Peptides?

Simply, research peptides are any peptides that are used in scientific research. In recent years, peptides have gained recognition as being highly selective and effective in therapeutic applications, all while being relatively safe and well tolerated in subjects and patients. As a result, there has been a huge uptick in interest in peptides for pharmaceutical research and development. With the promising potential that peptides present for medical applications, more and more research, study, and experimentation with peptides is necessitated in order to unlock the pharmaceuticals and therapeutics of today and tomorrow. Consequently, there has been a surge of demand for research peptides to fuel progress in these new avenues of research.


Research Peptides vs Medicines?

Importantly, research peptides are only made available for in-vitro study and experimentation. From the Latin for “in glass,” in-vitro refers to studies performed outside of the body. Hundreds of peptide therapeutics have been evaluated in clinical trials, and scientists and researchers around the globe are using research peptides in the lab to explore beyond the realm of traditional peptide design, pushing the boundaries to discover peptide variants that can be used as pharmaceuticals in the future. Already, there are over 60 peptide-based medicines on the market that have received approval from the US Food and Drug Administration (FDA). Among these are LupronTM, a treatment for prostate cancer, and VictozaTM, a treatment for type 2 diabetes. Both pharmaceuticals have achieved sales in the billions. However, it is essential to recognize that such FDA-approved drugs are NOT research peptides, they are just that: FDA-approved medications able to be prescribed by a healthcare professional for the treatment of a specific condition. Research peptides, on the other hand, are only intended for in-vitro study and research: they are not FDA approved for the treatment, prevention, or curing of any medical condition, disease, or ailment. Research peptides are those synthesized for study in the lab that can lead to new breakthroughs and future pharmaceuticals, but they become medicines only after undergoing rigorous study, clinical trial, and, crucially, the FDA approval process.


Research Peptides as Future Therapeutics

Over 7,000 naturally occurring peptides have been discovered. These peptides can often play vital roles in the human body as hormones, growth factors, neurotransmitters, ion channel ligands, and anti-infectives. Generally, peptides are effective and selective signaling molecules that bind to specific cell surface receptors, triggering intracellular effects. Additionally, in clinical trials, peptides have shown exceptional safety and tolerability in study subjects, while maintaining high selectivity and potency as well as a predictable metabolism. Consequently, peptides clearly present an enormous area of opportunity for therapeutic development.

Currently, the primary areas of disease fueling the research and use of peptide-based pharmaceuticals are metabolic diseases (such as type 2 diabetes) and oncology. The huge increases in obesity and type 2 diabetes in North America and other parts of the world have driven the development of peptide therapeutics for treatment of these conditions. Increases in cancer mortality and calls for alternatives to chemotherapy have spurred peptide research focused on oncological remedies. In addition, peptide research has expanded into the areas of infectious diseases, inflammation, and rare diseases. Research into peptides has also revealed excellent potential for their use in diagnostics and vaccination. Crucially, all of the research and study focused on unlocking the therapeutic potential of peptides for future medicines is reliant upon research peptides to serve as the basis for experimentation and development in the laboratory.