What is a peptide? Definition, types, functions and how peptides are made

A peptide is a chain of amino acids held together by amide bonds, which chemists and biologists call peptide bonds. Peptides sit between single amino acids and full-sized proteins: some are only two residues long, others run to several dozen. Many of the body’s signalling molecules are peptides, and so are a growing share of modern medicines.

This guide explains the definition, the naming of peptides by length, how a peptide differs from a protein, what peptides do in the body, how they are made, how peptide drugs are classified, and what “research use only” means for peptides sold to laboratories. It is written for students, the curious public and researchers who want one cited reference. Where a fact carries a number, a date or a mechanism, the source is linked in brackets.

What is a peptide?

The International Union of Pure and Applied Chemistry (IUPAC) defines a peptide as any compound produced by amide formation between a carboxyl group of one amino acid and an amino group of another, and notes that the amide bonds in peptides may be called peptide bonds [1]. Each amino acid built into the chain is called a residue, because a molecule of water is lost when the bond forms and “what remains of each amino acid” is the residue [1] [2].

Proteins and peptides draw on the same toolkit: 20 common amino acids occur in proteins [2]. When two amino acids join, the carboxyl group of one and the amino group of the next combine and release a water molecule, which is why peptide bond formation is described as a dehydration synthesis (condensation) reaction [2]. The chemistry of that bond, its planarity and how chemists make it, is covered in our guide to the peptide bond.

Every linear peptide has two ends. The end with a free amino group is the N-terminus and the end with a free carboxyl group is the C-terminus [2]. By convention, sequences are written with the N-terminal residue on the left [3], joined by hyphens, as in angiotensin II, Asp-Arg-Val-Tyr-Ile-His-Pro-Phe [4].

Dipeptides, tripeptides, oligopeptides and polypeptides

Peptides are named by the number of residues. IUPAC’s rule is that a multiplicative prefix before “peptide” gives the total number of residues, and that peptides with fewer than about 10 to 20 residues may also be called oligopeptides, while those with more are polypeptides [1]. The boundary is deliberately loose.

Term	Number of residues	Example	What the example is
Dipeptide	2	Glycylglycine	The simplest dipeptide, two glycine residues [5]
Dipeptide	2	Carnosine	β-alanyl-L-histidine, found in dietary red meat [6]
Dipeptide (methyl ester)	2	Aspartame	L-aspartyl-L-phenylalanine methyl ester, a sweetener [7]
Tripeptide	3	Glutathione	Glutamate linked through its side chain to cysteinylglycine [8]
Tripeptide	3	Thyrotropin-releasing hormone (TRH)	Pyroglutamyl-histidyl-prolinamide, a hypothalamic hormone [9]
Oligopeptide (nonapeptide)	9	Oxytocin	Cyclic peptide hormone, sequence CYIQNCPLG [10]
Oligopeptide (pentadecapeptide)	15	BPC-157	Synthetic research peptide, Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val [26]
Polypeptide	30 to 31	Active GLP-1, GLP-1(7-36)amide and GLP-1(7-37)	Incretin hormone; see GLP-1 agonists explained [11]
Polypeptide chains forming a protein	51 in total	Insulin	Two chains linked by two disulfide bridges [3]

What is a tripeptide?

A tripeptide is three amino acid residues joined by two peptide bonds. Glutathione is the best-known natural example: PubChem describes it as a tripeptide of glutamic acid attached through its side chain to the N-terminus of cysteinylglycine, with roles as an antioxidant and enzyme cofactor [8]. Thyrotropin-releasing hormone is another, made of L-pyroglutamyl, L-histidyl and L-prolinamide residues [9]. Because the first residue of glutathione uses its side-chain (γ) carboxyl group, glutathione also shows why IUPAC’s definition counts amide bonds that are not between alpha carbons [1].

How many different peptides are possible?

With 20 common amino acids, the number of possible linear sequences grows as 20 to the power of the chain length: 400 dipeptides, 8,000 tripeptides and 3.2 million pentapeptides, before counting non-standard residues, D-amino acids or modifications. This combinatorial space is one reason peptides are attractive starting points for drug discovery.

Peptide vs protein: what is the difference?

There is no single chemical difference. Both are chains of amino acids linked by peptide bonds. OpenStax’s biology text notes that “a polypeptide is technically a polymer of amino acids”, while the term protein is used for a polypeptide, or several combined, that has a distinct shape and function [2]. Proteins fold into secondary, tertiary and sometimes quaternary structure; losing that shape without breaking the chain is denaturation [2].

For regulation, length matters. The US FDA defines a protein as “any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size” [12]. Chains of 40 amino acids or fewer are therefore peptides for this purpose, which affects whether a product is regulated as a drug or a biological product in the United States.

Feature	Peptide	Protein
Building blocks	Amino acids joined by peptide bonds	Same
Typical length	Two to a few dozen residues	Longer, often hundreds of residues
US regulatory threshold	40 amino acids or fewer [12]	More than 40 amino acids [12]
Folded structure	Often flexible; some are cyclic or disulfide-constrained	Usually a defined three-dimensional fold [2]
Typical manufacture	Chemical synthesis (SPPS), sometimes recombinant	Mostly recombinant expression
Examples	Oxytocin, GLP-1, BPC-157	Haemoglobin, antibodies, enzymes

What do peptides do in the body?

Peptides do many jobs, and most of them involve signalling. The examples below are drawn from well-characterised biology; each is a description of physiology, not a claim about any product.

Hormones. Insulin, a protein hormone of two chains totalling 51 amino acids, helps regulate blood glucose [2] [3]. Oxytocin, a cyclic nonapeptide from the posterior pituitary, is the principal uterine-contracting and milk-ejecting hormone [10]. Thyrotropin-releasing hormone, a tripeptide released by the hypothalamus, stimulates the release of thyroid-stimulating hormone and prolactin from the anterior pituitary [9].

Gut hormones. Glucagon-like peptide-1 (GLP-1) is cleaved from proglucagon in intestinal L-cells. Its effects include glucose-dependent stimulation of insulin secretion, slower gastric emptying and reduced food intake [11]. Native GLP-1 has a half-life of around 1 to 2 minutes because the enzyme dipeptidyl peptidase-4 (DPP-4) removes its first two residues and the kidneys clear it [11]. That short life is the problem drug designers solved with long-acting analogues such as semaglutide and tirzepatide.

Host defence. Both animals and plants make broad-spectrum antimicrobial peptides that act against bacteria, fungi, viruses and protozoa [13].

Small metabolites. Glutathione conjugates to drugs to make them more soluble for excretion, acts as a cofactor for some enzymes, takes part in protein disulfide rearrangement and reduces peroxides [8]. Carnosine is reported to scavenge reactive oxygen species and lipid-peroxidation aldehydes in laboratory studies [6].

Neurotransmission. Oxytocin also acts as a neurotransmitter in the brain [10], and GLP-1 is made by a small population of neurons in the brainstem nucleus tractus solitarii [11].

How do peptides work?

Most peptide hormones act from outside the cell. They bind receptors on the cell surface, many of which are G protein-coupled receptors (GPCRs); GLP-1, GLP-2, glucagon and GIP, for example, all act through structurally related class B GPCRs [11]. A 2022 review, citing a 2018 analysis, noted that more than 90% of peptides in active clinical development targeted extracellular targets such as GPCRs [14]. Because peptides are relatively large and polar, few cross cell membranes on their own.

Common natural modifications

Many natural peptides are not simple linear chains of the 20 standard amino acids. Three modifications appear in the examples on this page:

• C-terminal amidation. The carboxyl end is capped as an amide, as in thyrotropin-releasing hormone, which ends in prolinamide [9], and in GLP-1(7-36)amide [11].
• N-terminal pyroglutamate. Thyrotropin-releasing hormone starts with a pyroglutamyl residue, a cyclised glutamate [9].
• Disulfide bridges and cyclisation. Oxytocin is a cyclic nonapeptide in which a disulfide bridge links cysteine 1 and cysteine 6 [10], and insulin’s two chains are held together by two disulfide bridges [3].

These features change how quickly a peptide is broken down and how it binds its receptor, which is why peptide chemists copy and extend them when designing drugs.

How are peptides made?

In living cells

Cells build peptides and proteins on ribosomes. Aminoacyl-tRNA synthetases first use ATP to load each amino acid onto its transfer RNA, and the energy for each peptide bond comes from that high-energy amino acid to tRNA link [15]. The bond itself is formed by peptidyl transferase, an RNA-based enzyme in the large ribosomal subunit [15]. Atomic structures published in 2000 showed that no protein side-chain atom lies closer than about 18 ångströms to the peptide bond being made, establishing that the ribosome is a ribozyme [16]. In E. coli, the translation machinery adds an amino acid roughly every 0.05 seconds [15].

Many bioactive peptides are then cut from larger precursors. Proglucagon, for example, is processed differently in the pancreas and the gut, giving glucagon in pancreatic alpha cells and GLP-1, GLP-2 and oxyntomodulin in intestinal L-cells [11].

The proglucagon example shows how one gene can yield several peptides with different jobs. The residue numbers below are positions in the precursor, as given in the 2019 review [11]; residue counts are calculated from those positions.

Peptide cut from proglucagon	Position in proglucagon [11]	Length (residues)	Main tissue
Glicentin-related pancreatic polypeptide (GRPP)	1 to 30	30	Pancreas
Glucagon	33 to 61	29	Pancreatic alpha cells
Oxyntomodulin	33 to 69	37	Intestinal L-cells
Glicentin	1 to 69	69	Intestinal L-cells
GLP-1	72 to 107/108	36 to 37 (before N-terminal trimming to the active 7-36/7-37 forms)	Intestinal L-cells and brainstem neurons
GLP-2	126 to 158	33	Intestinal L-cells
Major proglucagon fragment (MPGF)	72 to 158	87	Pancreas

Glucagon and GLP-1, made from the same precursor in different cells, have opposing effects on blood glucose [11]. Which peptides a cell makes depends on the prohormone convertase enzymes it expresses [11].

In the laboratory and in industry

The first synthesis of a polypeptide hormone, oxytocin, earned Vincent du Vigneaud the 1955 Nobel Prize in Chemistry [17]. Robert Bruce Merrifield’s solid-phase method, which anchors the growing chain to an insoluble support, earned the 1984 prize [18]. Today the majority of synthetic peptides are prepared by Fmoc solid-phase peptide synthesis (SPPS), which avoids the use of anhydrous hydrogen fluoride; classical Boc SPPS is now generally used only for specialist applications [19].

Some peptide drugs are made biologically instead. The peptide precursor of liraglutide, for example, is produced by recombinant DNA expression in the yeast Saccharomyces cerevisiae and then chemically modified [20]. For a full comparison of solid-phase, liquid-phase, hybrid and recombinant routes, see SPPS vs LPPS vs hybrid. For what a peptide becomes when it is made as a medicine ingredient, see what is a peptide API?

Peptide drugs: classes and how many are approved

Peptide medicines date back to insulin in the 1920s, when it was first isolated from livestock pancreata [14]. A 2021 perspective in Nature Reviews Drug Discovery reported that more than 80 peptide drugs have reached the market for conditions including diabetes, cancer, osteoporosis, multiple sclerosis, HIV infection and chronic pain [21]. A 2022 review in Signal Transduction and Targeted Therapy gave the same figure of more than 80 approved worldwide, counted 33 non-insulin peptide drugs approved since 2000, and reported more than 170 peptides in active clinical development [14].

Class (by origin or design)	Examples named in the reviews	Notes
Analogues of human hormones	Insulin analogues, octreotide (somatostatin), desmopressin (vasopressin), carbetocin (oxytocin)	Many approved peptide drugs are derived from natural hormones [14]
Incretin (GLP-1 family) agonists	Exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide	First GLP-1 receptor agonist approved by FDA in 2005 [14]
Peptides from venoms and other natural sources	Ziconotide, derived from the cone snail Conus magus and approved in 2004	Venoms remain an active discovery source [21] [14]
Gut-targeted peptides	Teduglutide (GLP-2 analogue), linaclotide (guanylate cyclase-C agonist)	Both approved by FDA in 2012 [14]
Antiviral fusion inhibitors	Enfuvirtide, a 36-residue peptide	Used in combination HIV-1 therapy [14]
Radiolabelled peptides	Lutetium-177 dotatate (treatment); radiolabelled somatostatin-like peptide conjugates such as octreoscan and depreotide (imaging)	Somatostatin-analogue conjugates for neuroendocrine tumours [14]

Why peptides need modification to become drugs

Natural peptides are chemically and physically unstable in the body, with a short half-life and fast elimination [14]. Common fixes include substituting D-amino acids or other non-natural residues, conjugating C14 to C18 fatty acids to prolong plasma circulation (used in liraglutide, semaglutide and insulin degludec), conjugation to serum albumin or immunoglobulin, PEGylation, cyclisation and, for oral delivery, co-formulation with permeation enhancers [14]. The GLP-1 agonists guide walks through these strategies for one drug class.

Research-use peptides explained

Many peptides are sold to laboratories as “research use only” (RUO) materials. The phrase comes from US device regulation: for an in vitro diagnostic product in the laboratory research phase, the labelling must bear the statement “For Research Use Only. Not for use in diagnostic procedures” [22]. FDA’s 2013 guidance on RUO labelling says the label is “meant to serve as a warning” against clinical use, and that labelling must be consistent with the manufacturer’s actual intended use [22].

That last point applies more widely. Under FDA regulations, the “intended uses” of an article refer to the objective intent of the persons legally responsible for its labelling, which may be shown by labelling claims, advertising matter, or the circumstances surrounding distribution [23]. An RUO statement on a vial does not change what a seller’s marketing shows the product is for. In the guidance’s own words, an inappropriately labelled RUO diagnostic product that lacks clearance or exemption is misbranded and adulterated under the Federal Food, Drug, and Cosmetic Act [22].

FDA has also published safety concerns about specific research peptides proposed for compounding. For BPC-157, the agency states that it “lacks sufficient information to know whether the drug would cause harm when administered to humans” and notes possible immunogenicity and peptide-related impurities; for thymosin beta-4 fragment (TB-500) it reports no human exposure data [24]. Our overviews of BPC-157 and TB-500 summarise the published research on each.

In the European Union, human research with an unauthorised medicine runs through clinical trial authorisation. The Clinical Trials Regulation (EU) No 536/2014 has applied since 31 January 2022, trials are authorised at national level by Member States, and sponsors submit applications through the Clinical Trials Information System (CTIS) [25].

Term	What it means	What it does not mean
Research use only (RUO)	Intended for laboratory research, not for diagnosis or treatment [22]	Approved, safe or legal for human or animal use
Investigational	Under study in authorised clinical trials [25]	Available outside the trial
Approved active ingredient (API)	Authorised for use in licensed medicines	That any vial of the same molecule is the approved product

Where to go next in the Peptide Research Library

The Peptide Research Library groups our guides by topic. For molecule-level detail, start with the overviews of semaglutide, tirzepatide, BPC-157 and TB-500. For chemistry, read what is a peptide bond; for manufacturing, SPPS vs LPPS; for the regulatory meaning of an active ingredient, what is a peptide API.

How Winhycare Pharma supplies peptides

Winhycare Pharma supplies research peptides as research-use-only material, with purity of ≥99% as stated in our product brochure, and offers custom peptide synthesis. Five molecules, semaglutide, tirzepatide, retatrutide, cagrilintide and BPC-157, are also supplied as API to licensed manufacturers; see the peptide API hub. US-DMF and CTD Module 3 support is available for semaglutide only. To discuss a research peptide, use our research peptide enquiry form; for API supply, use the peptide API enquiry form.

For laboratory research use only. Not for human or veterinary use.