What are peptides? A plain guide to peptides and research peptides

The short version

A peptide is a short chain of amino acids, the same building blocks that make up proteins, joined end to end by a particular kind of chemical link called a peptide bond. The body makes thousands of them, and many act as signals: hormones, neurotransmitters and parts of the immune system are peptides. Because short chains can be built in a laboratory with great precision, peptides are also made synthetically, both as licensed medicines and as chemicals for scientific research.

This guide explains what that means in practice: where the line between a peptide and a protein falls, how synthetic peptides are made and modified, what a "research peptide" is, how peptides differ from steroids, and how the quality of a peptide is measured. It does not cover the use of peptides in people. Everything we supply is for in-vitro laboratory research only.

Amino acids and the peptide bond

Amino acids are small organic molecules with an amino group (–NH₂) at one end, a carboxylic acid group (–COOH) at the other, and a side chain that gives each one its character. Twenty of them are coded for by DNA and used by every living cell to make proteins. Each has a three-letter and a one-letter abbreviation: glycine is Gly or G, histidine His or H, lysine Lys or K, and so on.

When the carboxyl group of one amino acid reacts with the amino group of another, they join through an amide link and release a molecule of water. In biochemistry that amide link is called a peptide bond. The IUPAC definition of a peptide is exactly this: an amide formed from two or more amino acids, by a bond from the carbonyl carbon of one to the nitrogen of the next, with formal loss of water [1]. The result still has a free amino group at one end, the N-terminus, and a free carboxyl group at the other, the C-terminus, so the chain can keep growing.

A peptide is written from the N-terminus to the C-terminus. GHK, for example, is glycine, then histidine, then lysine: a tripeptide, three amino acids long. Each amino acid in a chain is called a residue, because it is what remains after the water has been lost.

Peptides, polypeptides and proteins

The difference between a peptide and a protein is length, and the line is a convention rather than a law of chemistry.

Insulin, at 51 residues in two chains, is the usual example of a molecule that sits on the boundary. The more useful distinction is structural: proteins generally fold into a defined shape that their function depends on, while most short peptides are flexible in solution and take up a defined shape only when they bind to a target. That flexibility is also why short peptides are comparatively easy to make in a laboratory and comparatively easy to break down in the body.

What peptides do in the body

Most of the body's peptides are signals. They are released by one cell and recognised by a receptor on another, and because receptors are highly selective, a small change in sequence can change which receptor a peptide binds, or whether it binds at all. Some familiar groups are:

• Hormones. Insulin and glucagon in glucose regulation; oxytocin and vasopressin, nine residues each; growth-hormone-releasing hormone; the incretins GLP-1 and GIP released from the gut after a meal.
• Neuropeptides. Endorphins, enkephalins, substance P and many others that act as signals in the nervous system.
• Defence peptides. Antimicrobial peptides such as the defensins and cathelicidins, part of the innate immune system.
• Small peptides in tissue and blood. Glutathione, a tripeptide with an unusual linkage, is the main small-molecule antioxidant in cells. GHK was first isolated from human plasma in the 1970s and binds copper(II) with high affinity [2].

Many peptides are cut from larger precursor proteins. Others are fragments of larger proteins that turn out to have activity of their own; TB-500, for instance, is the seven-residue actin-binding segment of thymosin β4, a 43-residue protein.

How synthetic peptides are made

Almost every peptide sold for research, and many sold as medicines, is made by solid-phase peptide synthesis, a method published by Bruce Merrifield in 1963 that earned him the Nobel Prize in Chemistry in 1984 [3]. The first amino acid is attached by its C-terminus to a tiny insoluble resin bead. Each following amino acid is added in turn, with its own amino group temporarily protected so that only one link forms at a time; the protecting group is then removed, the beads are washed, and the cycle repeats. Because the growing chain stays fixed to the bead, excess reagents can simply be washed away. Modern synthesis uses Fmoc protecting groups and is largely automated.

When the chain is complete it is cut from the resin, usually with trifluoroacetic acid (TFA), which also removes the protecting groups from the side chains. The crude product is a mixture of the target peptide and closely related impurities: chains missing a residue, chains with a protecting group left on, chains damaged during cleavage. It is purified by preparative reversed-phase HPLC, and the purified fractions are freeze-dried (lyophilised) to the white or off-white powder that is supplied in a vial. Because TFA is present at the end of the process, most synthetic peptides are supplied as TFA salts unless they are exchanged to acetate.

Longer peptides and proteins are often made instead by recombinant expression, in which cells are engineered to produce them.

Modifications

A synthetic peptide does not have to be a copy of a natural one. Chemists modify sequences to make them more stable, more selective, or longer-lasting in a biological system. Common modifications include:

• End-capping. An acetyl group on the N-terminus or an amide on the C-terminus removes the charged ends and protects against enzymes that trim peptides from either end. TB-500 is N-acetylated; many research peptides are C-terminal amides.
• Unnatural amino acids. Mirror-image D-amino acids, or residues such as aminoisobutyric acid (Aib), resist the enzymes that break down natural sequences. Semaglutide carries Aib at position 8 for this reason.
• Lipidation. A fatty-acid chain attached through a linker lets a peptide bind to albumin in the blood. This is the main reason semaglutide and tirzepatide last far longer than native GLP-1.
• Cyclisation. Joining the ends, or linking two side chains, locks a peptide into a shape and protects it.
• Metal complexes. GHK-Cu and AHK-Cu are peptides supplied with copper(II) bound, and are characterised as the complex.

Each of these changes the molecular weight and the analytical signature, which is why the certificate for a modified peptide has to match the modified structure, not the native sequence. Every compound we supply has a monograph with its sequence, modifications and identifiers.

Peptides as medicines

Insulin was first used to treat diabetes in 1922, and peptides have been part of medicine ever since. More than 80 peptide drugs are approved worldwide, and peptides make up a growing share of new medicines [4]. They range from small molecules such as oxytocin and the somatostatin analogue octreotide to the lipidated GLP-1 receptor agonists semaglutide, liraglutide and tirzepatide.

Two properties explain both the appeal and the limits of peptides as drugs. They are highly selective, because they bind receptors in the same way the body's own signals do, and they are broken down into amino acids rather than into unusual metabolites. But they are also digested by the same enzymes that digest food protein, and they cross cell membranes poorly, which is why most licensed peptide medicines are not given as tablets and why so much chemistry goes into making them last longer.

A licensed peptide medicine is made under Good Manufacturing Practice, has been through clinical trials, has a marketing authorisation, and in the UK is usually prescription-only. The same molecule made outside that system is not a medicine, however pure it is.

What a research peptide is

A research peptide is a synthetic peptide sold as a chemical for laboratory work: cell and tissue assays, receptor-binding studies, analytical method development and similar in-vitro research. Some are sequences from the published literature that have never been developed as medicines; some are fragments or analogues of natural peptides; some are the same molecules as licensed drugs, supplied as reference material.

What makes something a research peptide is not the chemistry but the way it is supplied. It is not a licensed medicine, it is not made to pharmaceutical manufacturing standards, it carries research-use-only terms, and it is sold without claims about effects in people. In the UK that distinction is what keeps a research chemical outside medicines law, and our guide to research peptides and UK law explains the framework in detail. A seller that publishes dosing advice, "protocols" or before-and-after claims is presenting its product as a medicine, whatever its label says.

The peptides in our catalogue fall into a handful of research families:

• Growth-hormone secretagogues and related peptides, such as ipamorelin, CJC-1295, sermorelin and tesamorelin, which act at the GHRH and ghrelin receptors.
• Incretin and amylin analogues, such as semaglutide, tirzepatide and cagrilintide, studied at the GLP-1, GIP, glucagon and amylin receptors.
• Copper and melanocortin peptides, including GHK-Cu, AHK-Cu, MT-2 and PT-141.
• Peptide fragments, including BPC-157 and TB-500.
• Mitochondrial peptides and coenzymes, such as MOTS-c and SS-31.
• Neuropeptides and others, including semax, selank, KPV and thymosin α1.

Are peptides steroids?

No. Peptides and steroids are different classes of molecule. A steroid is a lipid built on a rigid skeleton of four fused carbon rings, made in the body from cholesterol; testosterone, oestradiol and cortisol are steroids. A peptide is a chain of amino acids. They are made differently, analysed differently, behave differently in the body and are regulated differently.

The confusion comes from the fact that both appear in discussions of sport and anti-doping. Anabolic steroids are Class C controlled drugs in the UK, and a small number of protein and peptide hormones, including growth hormone and chorionic gonadotrophin, are listed alongside them. Most research peptides are not controlled drugs, but many are on the World Anti-Doping Agency's Prohibited List. The UK law guide sets out which is which.

Are peptides safe?

There is no single answer, because "peptides" covers everything from a licensed medicine with years of clinical data behind it to a research chemical with none. A licensed peptide medicine has an established safety profile for its approved use under medical supervision. A research peptide has not been evaluated for use in people at all, and nothing about its purity changes that: a 99% pure vial of an untested compound is still an untested compound.

That is why research peptides are sold for in-vitro use only, and why we do not give advice on any other use. The question a laboratory can answer is narrower and more useful: is the material in the vial what the label says, at the purity it states? That is a question of analytical chemistry.

How peptide quality is measured

Because synthesis produces closely related impurities, a peptide's quality has to be measured batch by batch. The standard tests are:

• HPLC purity. Reversed-phase HPLC separates the target peptide from its impurities and reports the target as a percentage of the total peak area. Our guide to HPLC and LC-MS explains what that percentage does and does not tell you.
• Mass spectrometry identity. LC-MS or MALDI measures the molecular mass, which should match the expected mass for the sequence and its modifications.
• Net peptide content. A lyophilised powder contains peptide, bound water and counter-ion. Net content, measured by amino acid analysis or nitrogen determination, is the fraction that is peptide.
• Endotoxin. The LAL test measures bacterial endotoxin, which matters for cell-culture work.

A certificate of analysis brings these together for one batch. Our guide to reading a certificate of analysis walks through one, every batch we sell has its certificate in the public certificate register, and the buyer's checklist covers what to look for in any supplier.

Storage, in brief

Lyophilised peptides are stable for the few days of a UK delivery at room temperature and are kept refrigerated or frozen for longer storage. Once dissolved, a peptide is far less stable, and the right solvent depends on the sequence. The storage and stability and reconstitution solvents guides cover this compound by compound, and the peptide calculator handles the arithmetic for laboratory solutions.

Glossary

References

1. International Union of Pure and Applied Chemistry. "Peptides." Compendium of Chemical Terminology (the Gold Book). goldbook.iupac.org.
2. Pickart L, Thaler MM. Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nature New Biology. 1973;243(124):85–87.
3. Merrifield RB. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. Journal of the American Chemical Society. 1963;85(14):2149–2154.
4. Muttenthaler M, King GF, Adams DJ, Alewood PF. Trends in peptide drug discovery. Nature Reviews Drug Discovery. 2021;20(4):309–325.

Everything we supply is for in-vitro laboratory research only. Not for human or veterinary use.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.