What Are Peptides? Structure, Synthesis, Analytics, and Research
Peptides simply explained: amino acids, the peptide bond, how they differ from proteins, synthesis by SPPS, analytics with HPLC and MS, and the difference between cosmetic peptides and research peptides.
Peptides are short chains of amino acids linked to each other by peptide bonds. As a rule of thumb, chains of up to about 50 amino acids are called peptides, while longer, folded chains are called proteins. Peptides occur in all living organisms, for example as hormones and signaling molecules, and today can be routinely synthesized chemically.
Simply put: if amino acids are the letters, then peptides are short words and proteins are whole sentences or paragraphs. The order of the amino acids – the sequence – determines what shape a peptide takes and which molecules it interacts with. Exchanging even a single amino acid can change these properties considerably.
This introductory article explains how the peptide bond is formed, how peptides differ from amino acids and proteins, how they are produced and analyzed in the laboratory, in which research fields they are used, and how peptides in cosmetics differ from research peptides.
At a glance
- Definition: Peptides are chains of amino acids linked by peptide bonds (amide bonds).
- Distinction: The boundary to proteins is not defined uniformly; a range of around 50 amino acids is often cited.
- Synthesis: Solid-phase peptide synthesis (SPPS) was described by R. Bruce Merrifield in 1963.[1] He received the Nobel Prize in Chemistry for it in 1984.[2]
- Current standard: Fmoc-based solid-phase synthesis is considered the method of choice.[3]
- Analytics: Purity and identity are typically tested with HPLC and mass spectrometry.
- Significance: According to a review, more than 80 peptide drugs have reached the market since the introduction of insulin.[4]
- At SunPept: Research peptides as Vial or Pen, for laboratory purposes only.
What are peptides? Built from amino acids
The building blocks of all peptides are amino acids. Each amino acid has an amino group (–NH2), a carboxyl group (–COOH), and a side chain that gives it its individual properties – for example, whether it is hydrophilic, hydrophobic, acidic, or basic. Human proteins contain 20 standard proteinogenic amino acids, which are abbreviated with three-letter or one-letter codes, for example Gly (G) for glycine or Lys (K) for lysine.
A peptide has a direction: at one end there is a free amino group (N-terminus), at the other a free carboxyl group (C-terminus). By convention, sequences are always written from the N- to the C-terminus. The tripeptide GHK, for example, consists of glycine, histidine, and lysine in exactly this order.[7]
The peptide bond
The peptide bond forms when the carboxyl group of one amino acid reacts with the amino group of the next. A molecule of water is split off in the process – chemically, a condensation reaction. The result is an amide bond (–CO–NH–). It has partial double-bond character and is therefore largely planar, with only restricted rotation. This property shapes which spatial structures a peptide chain can adopt. Conversely, the peptide bond can be cleaved again by hydrolysis – i.e., with the uptake of water – for example enzymatically by proteases.
Nomenclature by chain length
| Term | Number of amino acids | Example |
|---|---|---|
| Dipeptide | 2 | Glycylglycine |
| Tripeptide | 3 | GHK (Gly-His-Lys) |
| Oligopeptide | a few, often up to about 10–20 | short signal peptides |
| Polypeptide | many, up to about 50 | Peptide hormones such as GLP-1 |
| Protein | usually well over 50, folded | Enzymes, structural proteins |
The boundaries between these terms are conventions and are not drawn consistently in the literature.
Peptide, protein, amino acid: the distinction
An Amino acid is a single building block. A Peptide is formed as soon as at least two amino acids are joined by a peptide bond. A Protein is a long polypeptide chain – or a complex of several chains – that folds into a defined three-dimensional structure.
So the difference lies not in the chemistry of the bond but in length and structure. Proteins typically form several levels of structure: the sequence (primary structure), local folding patterns such as the α-helix and β-sheet (secondary structure), the overall spatial shape (tertiary structure), and, where applicable, the assembly of several chains (quaternary structure). Short peptides, by contrast, are often flexible and only adopt a defined structure upon contact with their target molecule.
This has practical consequences: short peptides can be synthesized entirely chemically, whereas large proteins are usually produced biotechnologically in cells. The transition zone is fluid: even longer therapeutic peptides are now produced on a ton scale by solid-phase synthesis.[3]
Synthesis: how are peptides produced?
Merrifield and solid-phase synthesis
For a long time, synthesizing peptides in solution was laborious: after each coupling step, the intermediate had to be isolated and purified with considerable effort. In 1963, R. Bruce Merrifield described in the Journal of the American Chemical Society a new principle: the growing peptide chain is attached at its C-terminus to an insoluble polymer support. Excess reagents and by-products can then simply be washed away. Merrifield demonstrated the method with the synthesis of a tetrapeptide.[1] In 1984, he was awarded the Nobel Prize in Chemistry – for the development of a methodology for chemical synthesis on a solid matrix.[2]
The SPPS cycle
- Anchoring: The first amino acid is attached to the resin.
- Deprotection: The temporary protecting group on the amino group is removed.
- Coupling: The next, protected amino acid is activated and coupled.
- Washing: Excess reagents are washed out; the cycle starts again.
- Cleavage: At the end, the finished peptide is released from the resin and the side-chain protecting groups are removed.
Today, the Fmoc strategy (fluorenylmethoxycarbonyl as the temporary protecting group) is considered the method of choice. A review in the Journal of Peptide Science notes that high-quality Fmoc building blocks are available at low cost thanks to the ton-scale production of therapeutic peptides, and that many modified building blocks are commercially available.[3] Most peptides today are produced by SPPS.[5]
Analytics: how are purity and identity tested?
No synthesis step proceeds completely. A crude peptide therefore always contains by-products that must be removed by purification and detected by analytics. A review of impurities in peptide products describes, among others:[5]
- Deletion sequences: Peptides missing one amino acid, for example due to incomplete deprotection.
- Insertion sequences: Peptides with an additional amino acid, for example due to excess reagents.
- Racemization: Conversion of individual amino acids into their mirror image (diastereomeric impurities).
- Protecting-group adducts and oxidation products as well as counterions such as trifluoroacetate from synthesis and purification.
- Degradation products, for example from pyroglutamate or succinimide formation.
The authors point out that such impurities can already influence early functional studies and lead to false conclusions.[5] This is exactly why analytics are so important for research.
HPLC and mass spectrometry
| Method | Principle | What it shows |
|---|---|---|
| HPLC (usually reversed-phase) | Separation of components by hydrophobicity on a column | Proportion of the main peak in the total area, i.e., the chromatographic purity |
| Mass spectrometry (MS) | Determination of the mass-to-charge ratio of ionized molecules | Molecular mass and thus the identity of the peptide |
| LC-MS (coupled) | HPLC separation with direct MS detection | Identity of main and minor components |
An analysis report (Certificate of Analysis) summarizes these results for a specific batch. It is important that it refers to the specific batch delivered and states the method in a traceable way.
Research fields: where peptides are studied
Peptides are present in almost all areas of basic biomedical research. Since the introduction of insulin in the 1920s, peptide research has broadened considerably – from endogenous hormones to natural products to specifically designed molecules.[4][6] At SunPept, the research areas are organized into four lines:
- Metabolic Research: Receptor pharmacology of incretin receptors, e.g. with multi-receptor agonists such as retatrutide.
- Longevity: cellular energy metabolism and the biology of aging, for example around NAD+.
- Dermatology: skin biology and connective tissue, for example the copper peptide GHK-Cu.
- Tissue Research: preclinical models of tissue repair, for example with BPC-157 and TB-500 as components of blends.
A review in Nature Reviews Drug Discovery reports that more than 80 peptide drugs have reached the market since the introduction of insulin, including in diabetes, oncology, and osteoporosis.[4] This shows the relevance of this class of substances – but says nothing about individual research peptides that are not approved.
Peptides in cosmetics vs. research peptides
Many people know peptides from cosmetics, for example from serums or creams. Legally and in substance, however, this is a completely different product category from research peptides.
| Criterion | Peptides in cosmetics | Research peptides (RUO) |
|---|---|---|
| Legal framework in the EU | Cosmetics Regulation (EC) No 1223/2009 | not a cosmetic, not a medicinal product; classification depends on substance and purpose |
| Intended purpose | external application, including for cleansing, care, or protection | laboratory research only |
| Form | Ingredient of a formulation, usually in low concentration | Pure substance as a lyophilisate or solution |
| Use in humans | intended as a cosmetic | not intended |
The EU Cosmetics Regulation defines cosmetic products as substances or mixtures intended to be placed in contact with external parts of the human body, exclusively or mainly with a view to cleaning, perfuming, protecting, changing the appearance, keeping in good condition, or correcting body odors.[8] Research peptides do not fall under this definition: they are supplied without any cosmetic purpose, exclusively for scientific investigations. The same molecule – for example GHK-Cu – can therefore be regulated differently depending on the product and intended purpose.
What does “Research Use Only” mean?
“Research Use Only” (RUO) identifies substances intended exclusively for scientific and analytical investigations in the laboratory. They are not medicinal products, not dietary supplements, and not cosmetics, and they are not intended for human or veterinary use. Reputable suppliers label this clearly and make analysis documentation accessible. You'll find an overview of all research peptides in the Shop.
Frequently asked questions
What are peptides, simply explained?
Peptides are short chains of amino acids linked by peptide bonds. You can think of amino acids as letters, peptides as short words, and proteins as whole sentences. Peptides occur in all living organisms, for example as hormones or signaling molecules, and can be produced chemically in a targeted way in the laboratory.
What is the difference between a peptide and a protein?
Both consist of amino acids linked by peptide bonds. The difference lies in length and structure: peptides are shorter, as a rule of thumb up to about 50 amino acids, while proteins are longer and folded into a defined three-dimensional shape. The boundary is a convention and is not drawn consistently in the literature.
How is a peptide bond formed?
The carboxyl group of one amino acid reacts with the amino group of a second one. A water molecule is split off in the process, and an amide bond is formed. This bond is largely planar and has restricted rotation, which shapes the possible structure of the chain. It can be cleaved again by hydrolysis, for example with the help of enzymes.
How are peptides produced?
Today, synthetic peptides are mostly produced by solid-phase peptide synthesis (SPPS). R. Bruce Merrifield described the principle in 1963: the chain grows amino acid by amino acid on an insoluble resin. Today, the Fmoc strategy is standard. After synthesis, the peptide is cleaved off, purified, and analytically tested.
How is the purity of a peptide determined?
A combination of HPLC and mass spectrometry is common. HPLC separates the peptide from by-products and shows the proportion of the main peak; mass spectrometry confirms the identity via the molecular mass. An analysis report summarizes these results for a specific batch and should state the method in a traceable way.
Are peptides in cosmetics the same as research peptides?
No. Peptides in cosmetics are ingredients of formulations that fall under the EU Cosmetics Regulation and are intended for external application. Research peptides are pure substances supplied exclusively for laboratory investigations and are not intended for human use. The same molecule can be regulated differently depending on its intended purpose.
Sources
- 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
- The Nobel Prize in Chemistry 1984: Bruce Merrifield. NobelPrize.org (accessed October 21, 2026). nobelprize.org/prizes/chemistry/1984/summary/
- 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
- Muttenthaler M, King GF, Adams DJ, Alewood PF. Trends in peptide drug discovery. Nat Rev Drug Discov. 2021;20(4):309–325. doi:10.1038/s41573-020-00135-8
- 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
- Lau JL, Dunn MK. Bioorg Med Chem. 2018;26(10):2700–2707. doi:10.1016/j.bmc.2017.06.052
- Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int J Mol Sci. 2018;19(7):1987. doi:10.3390/ijms19071987
- Regulation (EC) No 1223/2009 of the European Parliament and of the Council of November 30, 2009 on cosmetic products, Art. 2(1)(a). OJ L 342 of December 22, 2009, p. 59. eur-lex.europa.eu/eli/reg/2009/1223/oj
Research Use Only: All peptides available from SunPept are intended exclusively for scientific laboratory research. They are not medicinal products, dietary supplements, or cosmetics and are not intended for human or veterinary use.
Research-grade peptides in the shop
Vial (lyophilized) or Pen (pre-dissolved), Janoshik analysis reports linked where available. Shipped from the EU to 25 countries. For research purposes only.