Peptides

A peptide is a short chain of amino acids joined by peptide bonds. Peptides sit between single amino acids and large proteins, and that middle position explains much of their importance. They are big enough to carry a specific chemical message, which is why peptides work as hormones, as signals in the brain, as defences in the skin and gut, and as venom toxins. They are also small enough for chemists to build: peptides have been made in the laboratory since 1901, and by 2021 more than 80 had been approved as medicines^[1].

What a peptide does depends on its sequence, the order of its amino acids. Each peptide bond forms between the carboxyl group of one amino acid and the amino group of the next, and a molecule of water is released. An unmodified linear peptide therefore has a free amino group at one end, called the N-terminus, and a free carboxyl group at the other, the C-terminus. Sequences are written from the N-terminus, and changing a single amino acid can change how the molecule behaves.

Peptides, oligopeptides and proteins

There is no sharp line between a peptide and a protein. By convention, chains of up to about 50 amino acids are called peptides and longer ones proteins; insulin, with 51 amino acids, is described as both. Chains of two to about ten residues are often called oligopeptides, and the shortest have their own names, such as dipeptides (two residues) and tripeptides (three).

Size also affects shape. Many proteins fold into relatively stable three-dimensional structures, while short peptides are often more flexible and may switch between different shapes. Flexibility has costs: a chain that must first settle into the right shape before it fits its target loses some binding strength in the process, and a loose chain is easier for enzymes to cut. Nature has found ways round both problems. Many natural peptides are modified in ways that change how long they survive and how they bind their targets. Oxytocin, for example, is closed into a ring by a disulfide bond between its two cysteines and ends in an amide rather than a free acid. Other peptides are joined head to tail into a ring, contain D-amino acids, or carry sugars, phosphate groups or fatty acids added after synthesis.

Some well-known peptides

The examples below run from two residues to fifty-one, and between them they cover most of what peptides do: taste, energy metabolism, signalling, pain, defence and food preservation.

Residue counts are for the mature peptide.

What peptides do

In the human body, peptides work mostly as messengers. Hormones such as insulin, glucagon and oxytocin travel in the blood. Neuropeptides such as substance P and the enkephalins act between nerve cells. Short peptides cut from larger precursors help regulate blood pressure (angiotensin) and salt and water balance (the natriuretic peptides). Other peptides defend the body: LL-37 and the defensins are among the antimicrobial peptides that kill bacteria on the skin and on mucous surfaces.

Peptides do not only carry signals inside a body. Other organisms use them to act on someone else: to paralyse prey, to deter predators or to stop competing microbes. They are, in short, weapons and tools; Peptides in nature describes what different organisms use them for. The venoms of cone snails, spiders, scorpions and bees are mixtures of peptides. One of the conotoxins, a 25-residue peptide from the cone snail Conus magus, is the basis of ziconotide, a painkiller approved in 2004^[1]. Fungi make cyclosporin A, a cyclic peptide that suppresses the immune system and is given after organ transplants.

Some of the same chemistry ends up in ordinary food. Aspartame is a dipeptide ester. Carnosine and anserine come from meat. Nisin keeps processed cheese and canned food from spoiling. Collagen peptides are made by breaking down collagen from skin and bone.

Peptides are also sold in skin-care products, and here the gap between laboratory and clinic is wide. The best known is the copper complex of the tripeptide GHK (glycyl-histidyl-lysine), and collagen peptides are sold both in creams and as supplements. Laboratory studies show effects on skin cells, but the clinical evidence is weak. A 2026 meta-analysis found only two good-quality trials of peptide creams^[2], and a 2025 meta-analysis found that collagen supplements improved the skin only in industry-funded trials, and not in trials without such funding or in those of high quality^[3].

A short history

Emil Fischer and Ernest Fourneau made the first synthetic peptide, glycylglycine, in 1901. Their route was indirect. They boiled glycine anhydride, a ring built from two glycine units, for about a minute in fuming hydrochloric acid, and the ring opened into the linear dipeptide^[4]. Fischer introduced the word "peptide" a year later.

Making a dipeptide was one thing; making a working hormone was another, and it took half a century. In 1953 Vincent du Vigneaud's group synthesised oxytocin, a nine-residue hormone closed into a ring by a disulfide bond, and showed that the synthetic product was as potent as the best natural preparations. Given to patients, it induced labour and milk release just as the natural hormone did^[5]. It was the first peptide hormone made in a laboratory, and du Vigneaud received the 1955 Nobel Prize in Chemistry.

Even after du Vigneaud, every intermediate had to be isolated and purified by hand, which limited how long a chain could be built. In 1963 Bruce Merrifield removed that bottleneck. He anchored the first amino acid to beads of an insoluble resin and built the chain on them one residue at a time. Instead of crystallising every intermediate, he filtered the beads and washed the impurities away. His first test was a simple tetrapeptide, Leu-Ala-Gly-Val^[6]. The method, which he named solid phase peptide synthesis, was soon automated and earned Merrifield the 1984 Nobel Prize in Chemistry. The full story is on the history of peptide science page.

How peptides are made

Cells make most peptides on the ribosome, usually as part of a longer precursor that enzymes later cut to size. Insulin, for example, is made as proinsulin, and the piece removed from the middle is called C-peptide. Some bacteria and fungi assemble peptides without ribosomes, using large enzyme complexes. This is how cyclosporin and many antibiotics come to contain unusual amino acids and rings.

In the laboratory the work has three stages: the chain is built one amino acid at a time, the crude product is purified, and the result is checked. Building is now almost always done by Merrifield's method, solid-phase synthesis. Because amino acids carry more than one reactive group, all but the two that should join are temporarily blocked by protecting groups at each step. Purification is most often done by reversed-phase HPLC. The check uses mass spectrometry, which confirms the mass and, with tandem methods, can also read the sequence, together with analytical HPLC, which shows how pure the peptide is. Before mass spectrometry, sequences were read one residue at a time by Edman degradation.

Peptides as medicines

Insulin came first. In January 1922 doctors at Toronto General Hospital treated a 14-year-old boy with severe diabetes using an extract of pancreas. The first injections, on 11 January, did little. A more concentrated extract, given daily from 23 January, cut the sugar in his urine sharply, and the boy became brighter and said he felt stronger^[7]. Today human insulin and its analogues are produced by genetically engineered microorganisms.

Peptides make attractive drugs because they bind their targets tightly and selectively. Their weak point is the one described earlier: a short, flexible chain is easy for enzymes to cut, so most peptides are broken down quickly in the blood and gut, and few can be taken by mouth. Chemists work around this by closing the chain into a ring, replacing some residues with D-amino acids, or attaching a fatty acid chain that binds to albumin in the blood and slows clearance. Semaglutide, a GLP-1 analogue given once a week, relies on the last of these.

By 2021 more than 80 peptide drugs had reached the market, more than 150 peptides were in clinical development and another 400 to 600 were in preclinical studies^[1]. Peptides are also measured in diagnostics: the C-peptide level shows how much insulin the pancreas is producing, and BNP, one of the natriuretic peptides, is used to assess heart failure. How peptides are developed into drugs is described in applications of peptides. A century after insulin, the same two properties still decide a peptide's fate as a medicine: how precisely it binds, and how long it survives. Both come back to the idea this page started with: a short chain of amino acids whose sequence, and whatever is added to it, determines what it can do.

References

1. Muttenthaler M, King GF, Adams DJ, Alewood PF (2021). Trends in peptide drug discovery. Nature Reviews Drug Discovery 20:309–325. DOI: 10.1038/s41573-020-00135-8
2. Nukaly HY, Halawani IR, Irtaza HM, Alturkistani T, Serafi MR, Alhawsawi W, et al. (2026). Oral and topical peptides for skin aging: systematic review and meta-analysis of randomized controlled trials. Frontiers in Medicine 13:1618306. DOI: 10.3389/fmed.2026.1618306
3. Myung S-K, Park Y (2025). Effects of collagen supplements on skin aging: a systematic review and meta-analysis of randomized controlled trials. The American Journal of Medicine. DOI: 10.1016/j.amjmed.2025.04.034
4. Fischer E, Fourneau E (1901). Ueber einige Derivate des Glykocolls. Berichte der Deutschen Chemischen Gesellschaft 34:2868–2877. DOI: 10.1002/cber.190103402249
5. du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG, Gordon S (1953). The synthesis of an octapeptide amide with the hormonal activity of oxytocin. Journal of the American Chemical Society 75:4879–4880. DOI: 10.1021/ja01115a553
6. Merrifield RB (1963). Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. Journal of the American Chemical Society 85:2149–2154. DOI: 10.1021/ja00897a025
7. Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (1922). Pancreatic extracts in the treatment of diabetes mellitus. Canadian Medical Association Journal 12:141–146.

This page describes the chemistry and biology of peptides. It is not medical advice.