What is a peptide? Amino acids, peptide bonds and how peptides are made

What is a peptide?

A peptide is a short chain of amino acids joined end to end by chemical links called peptide bonds. The US National Human Genome Research Institute puts the typical length at 2 to 50 amino acids; its glossary calls longer chains polypeptides, and proteins are built from one or more of them. Other conventions draw these lines differently, as the section on peptides and proteins shows.

Amino acids share a common core, an amino group and a carboxyl group, plus a side chain that differs from one to the next. Twenty standard amino acids make up most of the proteins of living things. The order in which they are joined, the sequence, is what makes one peptide different from another.

Peptide vs protein: where the line falls

There is no single cut-off. The IUPAC-IUBMB nomenclature rules call chains of fewer than about 10 to 20 residues oligopeptides and longer ones polypeptides. Chains of more than about 50 residues are usually called proteins, though the rules note that authors differ greatly on where that line sits.

Structure matters too. A protein usually folds into a specific three-dimensional shape, and many have more than one chain. Insulin shows how blurred the line is. It has 51 amino acids in two chains. Curated databases list those chains as peptides, while the Nobel Prize citation for the work on its structure calls insulin a protein.

Natural peptides: insulin, oxytocin and glutathione

Peptides occur throughout biology. Many, including peptide hormones such as insulin and oxytocin, are made like proteins. A ribosome reads messenger RNA copied from a gene and joins amino acids in the order it specifies, often as a longer precursor that is then cut. Others are built by enzymes. The three examples below describe natural roles only.

What do peptides do, and what are they used for?

In biology, peptides do many jobs. Some, like insulin and oxytocin, are peptide hormones that carry signals around the body. Others, like glutathione, take part in the chemistry inside cells. And every protein is built from one or more chains of amino acids linked by peptide bonds.

In research, synthetic peptides are useful because their sequence can be specified exactly. A laboratory can copy one section of a natural protein, change a single amino acid to study structure or binding, or use a well-characterised peptide as an analytical reference standard.

Some peptides are also made and supplied as medicines, under medicines law. A research-use label does not place a product outside that law. Whether something counts as a medicine depends on how it is presented as a whole and on what it does, so a label alone does not settle it.

How synthetic peptides are made

Synthetic peptides are usually made by solid-phase peptide synthesis (SPPS). The European Medicines Agency's guideline for peptide medicines describes it alongside solution-phase synthesis and fragment condensation, and acknowledges that most peptides will be made this way. Bruce Merrifield developed the method in the early 1960s and received the 1984 Nobel Prize in Chemistry for it. The growing chain is anchored to an insoluble resin, so excess reagents and by-products can be rinsed away after every step.

1. Anchoring: the first amino acid, at the C-terminal end, is attached to the resin.
2. Deprotection: a temporary protecting group is removed from the end of the chain, and the resin is washed.
3. Coupling: the next protected amino acid is joined by a new peptide bond; chain ends that failed to react may be capped.
4. Repetition: these steps are repeated for every amino acid in the sequence.
5. Cleavage: the finished chain is released from the resin and its side-chain protecting groups are removed, giving a crude peptide.

Small losses at each step add up, so the crude product contains near-miss molecules. The EMA guideline describes several kinds of these peptide-related impurities, including:

• Deletion sequences: one or more amino acids missing.
• Truncated sequences: chains stopped early by capping.
• Insertion sequences: an amino acid added more than once in a single coupling step.

How research peptides are named and supplied

Peptide names come from several traditions:

• Trivial names, such as insulin and oxytocin, which the nomenclature rules note are common for peptides of biological origin.
• Sequence codes, using the standard one-letter symbols: GHK is glycine, histidine, lysine, and GHK-Cu is that tripeptide bound to copper.
• Acronyms: MOTS-c stands for mitochondrial open reading frame of the 12S rRNA-c, a 16-amino-acid peptide.
• Product and blend names, which are not chemical descriptions. The label and laboratory report should name each compound and its amount.

Laboratory peptides are commonly supplied as freeze-dried powder in sealed vials. This shop supplies its compounds in a different format: already in solution in a prefilled pen, labelled with the total content in milligrams. Peptide pens explained covers how these pens are built and labelled. Storage follows the label, and how to store peptide pens covers temperature, light and moisture.

Why quality documentation matters

A peptide cannot be identified by looking at it. The correct material, a sequence missing one amino acid and a different compound altogether can all look like the same powder or clear liquid. Only analytical tests tell them apart.

A certificate of analysis should name the laboratory, batch number, test date, methods and results, typically HPLC purity and mass-spectrometry identity. The batch number should match the label. A report covers the identified tested sample only, and does not show sterility or endotoxin levels unless those were tested. Peptide testing and certificates of analysis explains each line of a report. This shop's published lab reports are records of tested samples; not every product has one, and a report does not verify every batch in stock.

Research peptides and UK medicines law