What is a peptide? A plain-English primer for researchers

In short: A peptide is a chain of amino acids joined by amide bonds, which chemists call peptide bonds. Short chains are called oligopeptides and longer ones polypeptides, and chains of more than about 50 residues are usually called proteins, though authors differ on the cut-off. Most synthetic peptides are made by solid-phase synthesis and freeze-dried after purification.

This primer is the starting point for our peptide science section and covers the chemistry the other posts assume. Shorter definitions of the terms used here are collected in our peptide glossary, and the later sections link to posts on how peptides are made, why they are freeze-dried and how sealed material is stored.

What is a peptide?

A peptide is a molecule formed when the carboxyl group of one amino acid reacts with the amino group of another to make an amide bond. That is the definition in the IUPAC-IUB nomenclature recommendations, which also call these amide links peptide bonds 1. The same recommendations extend the definition to isopeptide bonds, where the amide forms through a side-chain group rather than the main chain 1.

The word dates from the early 20th century. According to a 2014 review by Mäde et al., Emil Fischer synthesised the first dipeptide, glycylglycine, and coined the term “peptide” 2. A dipeptide has two amino acids; IUPAC notes that peptides with fewer than about 10 to 20 residues may be called oligopeptides and longer ones polypeptides 1.

What are amino acids?

Amino acids are the building blocks of peptides: small molecules that each carry an amino group (-NH2), a carboxyl group (-COOH) and a side chain. In the alpha-amino acids found in peptides, all three are attached to the same carbon atom, which IUPAC’s residue formula -NH-CHR-CO- reflects, with R standing for the side chain 1.

Mäde et al. note that only 20 amino acids are generally found in peptides and proteins, with a few rare exceptions, and that when cells make peptides on ribosomes these building blocks occur as L-enantiomers, one of two mirror-image forms. The 20 differ in their side-chain chemistry and polarity 2. In written sequences, residues are assumed to be L unless marked otherwise, and a D residue is shown with a D prefix, as in D-Ala 1.

Each amino acid has a three-letter and a one-letter symbol 1:

Amino acid	Symbols	Amino acid	Symbols
Alanine	Ala, A	Leucine	Leu, L
Arginine	Arg, R	Lysine	Lys, K
Asparagine	Asn, N	Methionine	Met, M
Aspartic acid	Asp, D	Phenylalanine	Phe, F
Cysteine	Cys, C	Proline	Pro, P
Glutamic acid	Glu, E	Serine	Ser, S
Glutamine	Gln, Q	Threonine	Thr, T
Glycine	Gly, G	Tryptophan	Trp, W
Histidine	His, H	Tyrosine	Tyr, Y
Isoleucine	Ile, I	Valine	Val, V

IUPAC also assigns U (Sec) to selenocysteine 1.

How does a peptide bond form?

A peptide bond forms when the carboxyl group of one amino acid joins the amino group of the next and a molecule of water is released. IUPAC describes it this way: when amino acids combine into a peptide, the elements of water are removed, and what remains of each amino acid is called a residue 1. Mäde et al. describe the same condensation reaction between a carboxylic acid and an amine 2.

The loss of water shows up in molecular weights. PubChem lists glycine (C2H5NO2) at 75.07 g/mol, water at 18.015 g/mol and glycylglycine (C4H8N2O3) at 132.12 g/mol 3. Two glycines weigh 150.14 g/mol; subtract one water (18.015 g/mol) and you get about 132.12 g/mol, the dipeptide. For a linear, unmodified chain the same rule holds at any length: its molecular weight is the sum of its free amino acids minus one water for each peptide bond.

Illustration: a short chain of linked beads standing in for amino acid residues.

The peptide bond is usually drawn as flat. Improta, Vitagliano and Esposito note that this planarity is traditionally explained by resonance, which gives the carbon-nitrogen bond partial double-bond character; in their 2011 computational study and survey of crystal structures, small distortions from planarity were more the rule than the exception 4.

How are peptide sequences written?

Peptide sequences are written from the N-terminus on the left to the C-terminus on the right. IUPAC defines the N-terminal residue as the one whose amino group is free (or capped, for example by acetylation) and the C-terminal residue as the one whose carboxyl group is free (or modified, for example as an amide) 1.

• Three-letter form. Symbols are joined by hyphens, and each hyphen stands for a peptide bond, as in Gly-Glu 1.
• One-letter form. The letter at the left end is the residue carrying the free amino group. IUPAC recommends this compact form for long sequences in tables and lists, not for running text 1.

Glycylglycine, for example, is Gly-Gly or GG. Glutathione is a useful example of an isopeptide bond: PubChem’s systematic name for it, C10H17N3O6S at 307.33 g/mol, shows its glutamic acid linked through the side-chain carboxyl at position 5, not the usual alpha carboxyl 3.

Where does a peptide end and a protein begin?

There is no single cut-off; the boundary depends on who is drawing it.

Source	Where the line is drawn
IUPAC-IUB recommendations	Oligopeptides below about 10 to 20 residues, polypeptides above; chains of specific sequence longer than about 50 residues are usually called proteins, but authors differ greatly 1
US Food and Drug Administration	For its biologics regulations, a protein is an alpha amino acid polymer of more than 40 amino acids, with associated chains counted together 5
Mäde et al., 2014 review	Peptides consist of up to 50 amino acids and generally lack the three-dimensional (tertiary) structure of proteins 2

The FDA definition is a US regulatory boundary, not a chemical one.

What modifications do synthetic peptides carry?

Many synthetic peptides differ from a plain chain of amino acids in small, deliberate ways that change their formula and mass.

• Capped ends. The N-terminal amino group can be acetylated, written with the prefix Ac-, and the C-terminal carboxyl can be an amide, written -NH2 1. In solid-phase synthesis, the linker attaching the chain to the resin decides whether the peptide ends in an acid or an amide 2.
• Disulfide bonds. Two cysteine side chains can join through a disulfide bond. IUPAC classes rings closed by a disulfide or another non-standard link as heterodetic cyclic peptides 1.
• D-amino acids. Synthetic sequences can include D residues, written with a D prefix 1.
• Counter-ions. Because side chains can be basic or acidic, peptides are often prepared as salts with counter-ions. Solid-phase synthesis followed by HPLC purification usually gives trifluoroacetate (TFA) salts 6. Our explainer on acetate vs TFA salts covers why that matters.

How are peptides made, dried and stored for research?

In cells, peptides and proteins are assembled on ribosomes 2. In the laboratory, most synthetic peptides are made by Fmoc solid-phase peptide synthesis 7, a method Merrifield first reported in 1963 8. Our guide to solid-phase peptide synthesis walks through each step.

After purification, acids used in the process, such as TFA and acetic acid, can be removed by lyophilisation, or freeze-drying 6. Our post on why research peptides are lyophilised explains the process.

Peptides also degrade over time. A 2014 review by D’Hondt et al. lists typical degradation routes, including beta-elimination and the formation of diketopiperazines, pyroglutamate and succinimides 9. Our post on how to store lyophilised peptides covers storage conditions for sealed material.

Illustration: sealed vials of lyophilised material in a laboratory rack.

How is a peptide’s identity checked?

A peptide’s identity and purity are usually checked with two complementary tools: chromatography, which separates the components of a sample, and mass spectrometry, which measures their mass. Mäde et al. note that soft-ionisation mass spectrometry, such as MALDI-TOF or electrospray, identifies a synthetic product and its by-products rapidly 2. Our explainers cover what an HPLC purity figure means, how mass spectrometry confirms identity and how to read a certificate of analysis. For the published literature, see how to read a peptide study.

Frequently asked questions

What is the difference between a peptide and a protein?

Mostly size, and the boundary is a convention. IUPAC-IUB recommendations say chains longer than about 50 residues are usually called proteins, while noting that authors differ greatly 1. The US FDA uses more than 40 amino acids in its regulatory definition of a protein 5. A 2014 review adds that peptides generally lack the tertiary structure of proteins 2.

How many amino acids are in a peptide?

At least two: a dipeptide such as glycylglycine has two 2. IUPAC notes that chains of fewer than about 10 to 20 residues may be called oligopeptides and longer ones polypeptides, and that the term protein is usually used above about 50 residues 1. There is no single agreed upper limit for a peptide.

What is a peptide bond?

A peptide bond is the amide bond that links the carboxyl group of one amino acid to the amino group of the next. Forming it releases one molecule of water, which is why a dipeptide such as glycylglycine (132.12 g/mol) weighs less than two glycines (2 × 75.07 g/mol) 3, 1. The bond has partial double-bond character and is close to flat, with small distortions common 4.

Which end of a peptide sequence is written first?

The N-terminus. By IUPAC convention, a sequence runs left to right from the residue with the free amino group (the N-terminus) to the residue with the free carboxyl group (the C-terminus) 1. So Gly-Glu means glycine at the N-terminus joined to glutamic acid at the C-terminus. One-letter sequences follow the same rule.

Why do synthetic peptides contain counter-ions such as TFA?

Peptides with charged side chains are often obtained as salts paired with counter-ions. Trifluoroacetic acid (TFA) is used to cleave peptides from the resin at the end of solid-phase synthesis and in HPLC purification, so peptides are usually obtained as trifluoroacetate salts unless the counter-ion is exchanged, for example for acetate 6. See acetate vs TFA salts for more.

References

1. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature and symbolism for amino acids and peptides. Recommendations 1983. Biochem J. 1984;219(2):345-373. doi:10.1042/bj2190345. PMID: 6743224. PMCID: PMC1153490. Web version: https://iupac.qmul.ac.uk/AminoAcid/, accessed 28 September 2026. [nomenclature recommendation]
2. Mäde V, Els-Heindl S, Beck-Sickinger AG. Automated solid-phase peptide synthesis to obtain therapeutic peptides. Beilstein J Org Chem. 2014;10:1197-1212. doi:10.3762/bjoc.10.118. PMID: 24991269. PMCID: PMC4077397. [narrative review]
3. PubChem. Compound summaries for glycine (CID 750), glycylglycine (CID 11163), water (CID 962) and glutathione (CID 124886). National Center for Biotechnology Information. Accessed 28 September 2026. [chemical database]
4. Improta R, Vitagliano L, Esposito L. Peptide bond distortions from planarity: new insights from quantum mechanical calculations and peptide/protein crystal structures. PLoS One. 2011;6(9):e24533. doi:10.1371/journal.pone.0024533. PMID: 21949726. PMCID: PMC3174960. [computational and structural database study]
5. US Code of Federal Regulations. 21 CFR 600.3, Definitions, paragraph (h)(6). Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-F/part-600/subpart-A/section-600.3. Accessed 28 September 2026. [US regulation]
6. Sikora K, Jaśkiewicz M, Neubauer D, et al. The Role of Counter-Ions in Peptides-An Overview. Pharmaceuticals (Basel). 2020;13(12):442. doi:10.3390/ph13120442. PMID: 33287352. PMCID: PMC7761850. [narrative review]
7. Behrendt R, White P, Offer J. Advances in Fmoc solid-phase peptide synthesis. J Pept Sci. 2016;22(1):4-27. doi:10.1002/psc.2836. PMID: 26785684. PMCID: PMC4745034. [narrative review]
8. Merrifield RB. Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. J Am Chem Soc. 1963;85(14):2149-2154. doi:10.1021/ja00897a025. [original method report]
9. D’Hondt M, Bracke N, Taevernier L, et al. Related impurities in peptide medicines. J Pharm Biomed Anal. 2014;101:2-30. doi:10.1016/j.jpba.2014.06.012. PMID: 25044089. [narrative review]