Amino Acids: The Building Blocks of Peptides Explained

Amino acids are the building blocks of peptides and proteins. Each one is a small molecule with an amino group, a carboxyl (acid) group, and a distinctive side chain. Link amino acids together in a specific order and you get a peptide. The order and chemistry of those side chains decide what the peptide looks like and what it does. This guide covers the basics: structure, the 20 standard amino acids, "essential" amino acids, and how amino acids join into chains.

Key Takeaways

• An amino acid contains an amino group, a carboxyl group, and a side chain (often written "R") attached to a central carbon [1][2].
• Twenty amino acids are directly encoded by the genetic code. Selenocysteine and pyrrolysine are sometimes called the 21st and 22nd [2][3].
• Nine amino acids are considered nutritionally indispensable (essential) for humans because the body cannot make them in sufficient amounts [4].
• Amino acids in proteins are the L-form. Glycine is the exception because it has no mirror-image form [2][5].
• When amino acids join, water is released and each unit in the chain becomes a "residue". Chains are written from the N-terminus to the C-terminus [1].

What Is an Amino Acid?

Chemically, amino acids are organic compounds containing both amino and acid groups [5]. The ones that build peptides and proteins are alpha-amino acids: the amino group and the carboxyl group are attached to the same carbon atom, called the alpha carbon. A third group, the side chain, also hangs off that carbon, and it is what makes each amino acid different [2].

A simple way to picture it:

• Amino group (–NH₂): one "hand" that can link to the next amino acid
• Carboxyl group (–COOH): the other "hand"
• Side chain (R): the personality. It might be a single hydrogen atom (glycine), a sulfur-containing group (cysteine, methionine), a ring structure (phenylalanine, tryptophan), or a charged group (lysine, aspartic acid) [2]

The 20 Standard Amino Acids

The IUPAC–IUB nomenclature recommendations list the alpha-amino acids that are incorporated into proteins under genetic (mRNA) direction, along with standard three-letter and one-letter symbols [2]. Japan's Ministry of Health, Labour and Welfare, in its dietary reference intake documentation, likewise describes proteins as being made of 20 different amino acids directly encoded by codons [6].

Symbols from IUPAC–IUB [2]. Indispensable and conditionally indispensable classifications from the WHO/FAO/UNU expert report [4].

Beyond these 20, selenocysteine (symbol Sec or U) and pyrrolysine are known as the 21st and 22nd amino acids. They are inserted into some proteins during translation through special decoding mechanisms [3].

The one-letter code is mainly used to write long sequences compactly. IUPAC–IUB recommends it for tables and sequence comparisons rather than ordinary text [2].

Essential vs. Non-Essential Amino Acids

"Essential" is a nutritional term, not a measure of importance. Every amino acid matters. The difference is whether the body can make enough of it.

• Indispensable (essential): A 2007 report from a joint WHO/FAO/UNU expert consultation lists nine nutritionally indispensable amino acids: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine [4].
• Conditionally indispensable: The same report notes that some amino acids, such as cysteine, tyrosine, glycine, arginine, glutamine, and proline, can become indispensable under particular physiological or disease conditions [4]. (The report also lists taurine, which is not one of the 20 protein-building amino acids.)
• Dispensable (non-essential): Amino acids the body can normally make from other compounds.

The essential/non-essential idea dates back more than a century to nitrogen-balance experiments in animals and later in humans [5].

Mirror Images: L- and D-Amino Acids

Most amino acids are chiral: like your left and right hands, they come in two mirror-image forms that cannot be superimposed, called L and D. IUPAC–IUB notes that for the chiral amino acids, only the L-form is used in protein biosynthesis [2]. Glycine, whose side chain is just a hydrogen atom, is the only standard amino acid without a mirror-image form [5][7].

This matters for peptide quality. If the wrong mirror-image form slips into a synthetic peptide, the result is a stereoisomer, a molecule with the same atoms and mass but a different 3D shape. The European Medicines Agency (EMA) identifies stereoisomers, including those formed by epimerization during synthesis, as important impurities in synthetic peptides [7].

Chemists sometimes use D-amino acids on purpose. Swapping L-amino acids for D-forms at vulnerable positions can make a peptide harder for enzymes to break down and extend its half-life [8][9]. See Peptide Half-Life Explained.

Side Chains: The Chemistry That Shapes Behavior

Side chains are commonly grouped by polarity [10]:

• Nonpolar (hydrophobic): e.g., leucine, valine, phenylalanine
• Polar, uncharged: e.g., serine, threonine, asparagine
• Positively charged (basic): e.g., lysine, arginine
• Negatively charged (acidic): aspartic acid, glutamic acid

These properties shape how a peptide folds, dissolves, and binds to targets. They also shape how it behaves in the lab. Reversed-phase HPLC, for example, separates peptides largely by overall hydrophobicity [10]. Read more in HPLC Testing Explained.

Certain side chains are also chemically vulnerable. The EMA guideline highlights oxidation of cysteine and methionine and deamidation among potential peptide degradation pathways [7]. See How Peptides Degrade.

How the Building Blocks of Peptides Join: The Peptide Bond

When two amino acids combine, the carboxyl group of one reacts with the amino group of the other to form an amide bond (the peptide bond), and the elements of water are removed [1]. What remains of each amino acid in the chain is called an amino acid residue [1].

Every linear peptide has two ends [1]:

• the N-terminus, with a free (or modified) amino group
• the C-terminus, with a free (or modified) carboxyl group

By convention, sequences are written from the N-terminus on the left to the C-terminus on the right [2]. So "GAV" and "VAG" are different peptides, even though they contain the same three amino acids.

Why sequence matters: a real example

Tiny sequence differences can change biology. When researchers studied the gut hormone GLP-1, they found that its N-terminal region is susceptible to cleavage by the enzyme dipeptidyl peptidase-IV (DPP-IV), while the related peptide exendin-4 is resistant. The difference comes down to a single amino acid at the second position: GLP-1 has an alanine there, and exendin-4 does not [11].

Amino Acids and Peptide Testing

Because a peptide is defined by its amino acids and their order, several laboratory tests focus on them:

• Amino acid analysis breaks a peptide down and measures its amino acid composition. The EMA notes that it usually complements the characterization of synthetic peptides and can also contribute to content determination [7].
• Mass spectrometry confirms the peptide's mass and can confirm its sequence [7]. Note that some amino acids share the same atomic formula. Leucine and isoleucine are isomers [2], so they cannot be told apart by mass alone. See Mass Spectrometry for Peptides.
• Impurity profiling looks for sequence errors such as deletion sequences (a missing amino acid), insertion sequences (an extra one), and incorrect amino acids [7].

For the terms used in lab reports, see the Peptide Terminology Glossary.

Frequently Asked Questions

How many amino acids are there?

Many other amino acids exist (IUPAC–IUB lists additional common ones [2]), but 20 are directly encoded by the standard genetic code for building proteins [2][6]. Selenocysteine and pyrrolysine are sometimes counted as the 21st and 22nd [3].

What are the nine essential amino acids?

Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine, according to the WHO/FAO/UNU expert report [4].

What is the difference between an amino acid and a peptide?

An amino acid is a single building block. A peptide is two or more amino acids linked by peptide bonds [1].

Why are amino acids "L" and not "D"?

Proteins in living organisms are built from L-amino acids [2]. Some free amino acids can occur naturally in the D-form [5], and D-amino acids are sometimes used deliberately in synthetic peptides, for example to resist enzyme breakdown [8][9].

What is an amino acid residue?

It is what remains of an amino acid once it has been built into a peptide chain and water has been removed during bond formation [1].

References

1. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature and Symbolism for Amino Acids and Peptides (Recommendations 1983), sections 3AA-11 and 3AA-12. Pure Appl Chem. 1984;56:595–624. https://doi.org/10.1351/pac198456050595 ↗ (web: https://iupac.qmul.ac.uk/AminoAcid/A1113.html ↗)
2. IUPAC-IUB JCBN. Nomenclature and Symbolism for Amino Acids and Peptides, section 3AA-1 (Table 1) and sections 3AA-20 to 3AA-21 (one-letter system). https://iupac.qmul.ac.uk/AminoAcid/AA1n2.html ↗ and https://iupac.qmul.ac.uk/AminoAcid/A2021.html ↗
3. Yuan J, O'Donoghue P, Ambrogelly A, et al. Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl-tRNA formation systems. FEBS Lett. 2010;584(2):342–349. https://doi.org/10.1016/j.febslet.2009.11.005 ↗
4. Joint WHO/FAO/UNU Expert Consultation. Protein and Amino Acid Requirements in Human Nutrition. WHO Technical Report Series No. 935. Geneva: World Health Organization; 2007. https://iris.who.int/handle/10665/43411 ↗
5. Hou Y, Wu G. Nutritionally essential amino acids. Adv Nutr. 2018;9(6):849–851. https://doi.org/10.1093/advances/nmy054 ↗
6. Ministry of Health, Labour and Welfare (Japan). Dietary Reference Intakes for Japanese (2025), "Protein" chapter (English version). https://www.mhlw.go.jp/content/10900000/001580196.pdf ↗
7. European Medicines Agency. Guideline on the Development and Manufacture of Synthetic Peptides (EMA/CHMP/CVMP/QWP/367182/2025). https://www.ema.europa.eu/en/development-manufacture-synthetic-peptides-scientific-guideline ↗
8. Werle M, Bernkop-Schnürch A. Strategies to improve plasma half life time of peptide and protein drugs. Amino Acids. 2006;30(4):351–367. https://doi.org/10.1007/s00726-005-0289-3 ↗
9. Wang L, Wang N, Zhang W, et al. Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther. 2022;7(1):48. https://doi.org/10.1038/s41392-022-00904-4 ↗
10. Mant CT, Chen Y, Yan Z, et al. HPLC analysis and purification of peptides. Methods Mol Biol. 2007;386:3–55. https://doi.org/10.1007/978-1-59745-430-8_1 ↗
11. Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide. Front Endocrinol (Lausanne). 2019;10:155. https://doi.org/10.3389/fendo.2019.00155 ↗

Educational disclaimer: This article is for general educational purposes only. It is not medical, nutritional, legal, or regulatory advice, and it does not recommend or describe the use of any product. For health or nutrition questions, consult a qualified healthcare professional. For regulatory questions, consult the relevant regulatory authority in your jurisdiction.