What is a peptide?

Every peptide is made from amino acids. Each amino acid has the same backbone, an amino group (-NH₂) at one end and a carboxyl group (-COOH) at the other, with a central carbon carrying a side chain. The side chain is what makes each amino acid different: it can be small (glycine's is a single hydrogen atom), acidic, basic, water-loving or oily.

Living things build their proteins mainly from twenty standard amino acids, plus selenocysteine, sometimes called the 21st. Biochemists give each one a three-letter abbreviation (Gly, Ala, Lys) and a one-letter code (G, A, K), agreed by the international nomenclature committees of IUPAC and IUBMB. Our amino acid codes table lists them all.

Most amino acids also come in two mirror-image forms, L and D. Nature uses the L form almost exclusively; synthetic peptides sometimes include a D amino acid on purpose, and the notation marks it.

A peptide bond forms when the carboxyl group of one amino acid reacts with the amino group of the next. A molecule of water is released, and the two are joined by an amide link (-CO-NH-). Chemists call this a condensation reaction.

Three properties of the bond explain a lot about how peptides behave:

• It is flat and rigid. The bond has partial double-bond character, so the atoms around it sit in one plane and don't rotate freely. Chains fold by twisting at the bonds either side of it.
• It gives the chain a direction. One end of every peptide carries a free amino group (the N-terminus) and the other a free carboxyl group (the C-terminus). By convention, sequences are written from the N-terminus on the left to the C-terminus on the right.
• It is strong, but not permanent. Peptide bonds are stable in a dry powder. In water, over time, and faster with heat, extremes of pH or enzymes, they can break again (hydrolysis). That is one reason peptides are stored dry and cold.

There is no official cut-off, which is why you will see different numbers quoted. The working conventions, from the smallest types of peptide upwards, are:

The boundary is genuinely fuzzy. Insulin is a good example: it is made of two chains, 21 and 30 amino acids long, held together by disulfide bridges. Some textbooks call it a peptide hormone and others a small protein. Both are fair.

The same words turn up in cosmetic ingredient names. Acetyl hexapeptide-8 is a chain of six amino acids, and acetyl octapeptide-3 a chain of eight: the same six with two more added at the end.

At the small end, an everyday example is the sweetener aspartame, which is the methyl ester of a dipeptide made from aspartic acid and phenylalanine. Collagen peptides sold as food supplements are fragments of the protein collagen, broken down into shorter chains.

In living things, peptides do a wide range of jobs. Many hormones and signalling molecules are peptides: insulin and glucagon, the two hormones that keep blood sugar in balance, are both peptides. So are the defensins, small antimicrobial peptides that form part of the body's first line of defence. What any individual peptide does depends entirely on its sequence and shape.

We deliberately go no further than that. We supply research-grade peptides for laboratory work, and we don't describe any of them in terms of effects in the body. If your question is about using a peptide, the right person to ask is a doctor or pharmacist, and our guide Are peptides legal in the UK? explains why.

The same word turns up in four very different places, which is why searches for it are so mixed:

• Skincare. Cosmetic peptides such as copper tripeptide-1 and acetyl octapeptide-3 are ingredients in creams and serums. On a label they appear under their INCI names, the standard names used for cosmetic ingredients.
• Food. Collagen peptides are sold as powders and drinks, regulated as food.
• Medicine. A number of licensed medicines are peptides. They are prescribed and supplied through the medicines system like any other medicine.
• Laboratories. Research groups use synthetic peptides as reagents and reference materials in experiments.

Each of those uses has its own rules in the UK. For skincare ingredients, see cosmetic peptides for skincare brands; for the legal position overall, see Are peptides legal in the UK?.

A peptide's sequence is written left to right, N-terminus to C-terminus, using either code:

• Three-letter: Gly-His-Lys
• One-letter: GHK

Chemical changes to the ends or the ring structure are written as prefixes and suffixes:

Our own name is a peptide written this way: U-K-M-A-S-T-E-R-P-E-P-T-I-D-E-S, sixteen residues, starting with selenocysteine. Read the story, or put the sequence into our peptide mass calculator.

Most peptides sold today are made by solid-phase peptide synthesis, a method developed by Bruce Merrifield, who received the Nobel Prize in Chemistry in 1984 for it. In outline:

1. The first amino acid (the C-terminal one) is attached to a tiny resin bead.
2. The next amino acid, with its reactive groups temporarily blocked by protecting groups, is added and coupled to it.
3. The protecting group on the new end is removed, and the cycle repeats, one amino acid at a time, building the chain from the C-terminus towards the N-terminus.
4. The finished chain is cut from the bead and its side-chain protecting groups are removed.
5. The crude peptide is purified, usually by reversed-phase HPLC.
6. The purified peptide is freeze-dried (lyophilised) to a dry powder, which is the form it is normally stored and shipped in.

Very long chains are often better made by recombinant methods, in which engineered cells produce the chain, but for peptides of up to a few dozen residues chemical synthesis is the norm.

Two tests do most of the work, and a good certificate of analysis reports both:

• HPLC purity. High-performance liquid chromatography separates the target peptide from related impurities, such as chains with a missing or extra amino acid. Purity is the share of the target peptide among everything the detector sees.
• Mass spectrometry. Measures the molecular mass, which confirms that the main peak really is the intended sequence.

A peptide powder is never 100% peptide by weight: it also holds bound water and counter-ions such as acetate or trifluoroacetate. That is measured as net peptide content, a different number from purity. Peptide purity and net peptide content explains the difference, and How to read a certificate of analysis walks through a real certificate line by line.

Dry peptide powders absorb moisture from the air, and some amino acids (cysteine, methionine and tryptophan in particular) oxidise easily. That is why laboratory suppliers advise storing lyophilised peptides cold, typically around −20 °C or below, tightly closed and away from light, and letting a vial warm to room temperature before opening it. Peptides keep far less well in solution. Our storage and handling guide has the details.