Introduction to Peptides

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.