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Amino Acids and the Peptide Bond

For medical students2 min readUpdated 2026-10-10

Proteins are linear polymer molecules composed of 20 proteinogenic $\alpha$-amino acids as monomers. Their specific set and sequence are strictly encoded in DNA, which directly determines the spatial structure of the protein and its biological function in the organism.

Genetic DeterminationThe sequence of the 20 $\alpha$-amino acids in a protein is strictly dictated by genes within the DNA molecule.

Peptide BondFormed between the amino and carboxyl groups with the release of a water molecule ($H_2O$).

Proline ExceptionAn imino acid that forms a cyclic structure lacking a hydrogen atom on the nitrogen.

Reading RulePeptide chains are always written and read in the direction from the N-terminus to the C-terminus.

Biological Role and General Characteristics of Proteins

Proteins are polymers whose structural units are 20 $\alpha$-amino acids. Biochemistry follows the strict "Structure-Function" principle: each protein molecule possesses a unique spatial configuration perfectly tailored to perform a specific task.

An organism's individual set of proteins is of paramount importance. It determines:

Human phenotypic traits.
The presence of hereditary diseases (in case of genetic code errors).
Predisposition to various pathologies.

Structure of $\alpha$-Amino Acids

All proteinogenic amino acids share a uniform structural plan. At the center of the molecule is an $\alpha$-carbon atom, to which the main functional groups and a unique side chain are attached.

Under physiological conditions, these functional groups are ionized:

The $\alpha$-amino group carries a positive charge ($-NH_3^+$).
The $\alpha$-carboxyl group carries a negative charge ($-COO^-$).

The third component is the side chain ($R$), attached to the same $\alpha$-carbon atom. Amino acids differ from one another exclusively in the structure, size, and physicochemical properties of their side chains.

Side Chain Classification and Solubility

The physicochemical properties of side chains determine the ability of amino acids to hydrate—that is, to interact with water molecules and dissolve in them.

1. Hydrophilic Side Chains These side chains actively interact with water due to charged or polar groups:

Anionic groups: carboxyl ($-COO^-$).
Cationic groups: amino group ($-NH_3^+$), imino group ($=NH^+$), and guanidino group ($-NH_2-C=NH_2^+$).
Polar uncharged groups: hydroxyl ($-OH$), amide ($-CONH_2$), and thiol/sulfhydryl ($-SH$).

2. Hydrophobic Side Chains These groups are incapable of hydration. Nonpolar hydrophobic side chains include methyl groups ($-CH_3$), aliphatic chains, and aromatic rings.

Peptide Bond Formation and Peptide Structure

Amino acids are linked into linear polymers (proteins) via the peptide bond.

Its formation mechanism involves the chemical interaction of the $\alpha$-carboxyl group of one amino acid with the $\alpha$-amino group of another amino acid. This process is accompanied by the elimination of a single water molecule ($H_2O$).

As a result, a peptide backbone is formed—a long chain of repeating $-NH-CH-CO-$ groups. Side chains ($R_1, R_2, R_3...$) project outward from this backbone. Each individual monomer within such a chain is called an amino acid residue.

Every peptide has two distinct ends:

N-terminus (N-terminal residue): contains a free $\alpha$-amino group.
C-terminus (C-terminal residue): contains a free $\alpha$-carboxyl group.

Unique Properties of Proline

Among the 20 protein monomers, proline occupies a special place. According to chemical classification, it is not an amino acid, but an imino acid.

The side chain of proline forms a closed ring: it is simultaneously bound to both the $\alpha$-carbon atom and the imino group. Because of this cyclic structure, the peptide bond formed by proline's imino group differs significantly from standard peptide bonds—the nitrogen atom within the peptide group completely lacks a hydrogen atom.

Mnemonic

To avoid confusing the direction of reading proteins, remember: read just like writing the word "N-to-C" starting from the N-terminus to the C-terminus.

Frequently asked questions

Which specific amino acids are classified as hydrophobic?

Hydrophobic (nonpolar) amino acids are those whose side chains contain aliphatic hydrocarbon chains or aromatic rings without polar groups. They include:

Alanine (Ala) — has an aliphatic side chain.
Valine (Val) — has an aliphatic side chain.
Leucine (Leu) — has an aliphatic side chain.
Isoleucine (Ile) — has an aliphatic side chain.
Phenylalanine (Phe) — contains an aromatic ring.
Tryptophan (Trp) — contains an aromatic ring.
Methionine (Met) — contains a nonpolar thioether group.
Proline (Pro) — is a cyclic imino acid.

Which proteinogenic amino acids contain a hydroxyl OH-group in their side chain?

The following proteinogenic amino acids contain a hydroxyl group ($-OH$) in their side chain:

Serine (Ser) — side chain $-CH_2OH$; classified as a hydroxy amino acid.
Threonine (Thr) — side chain $-CH(OH)CH_3$; classified as a hydroxy amino acid.
Tyrosine (Tyr) — contains a hydroxyl group in its side chain; classified as an aromatic amino acid.

Serine, threonine, and tyrosine are classified as hydrophilic uncharged (polar) amino acids.

Which amino acids have an additional carboxyl group in their side chain (acidic amino acids)?

Hydrophilic anionic (acidic amino acids) possess an additional carboxyl group in their side chain:

Aspartic acid (Asp) — a carboxy amino acid.
Glutamic acid (Glu) — a carboxy amino acid.

Their side chains feature a $-COOH / -COO^-$ group, making them negatively charged hydrophilic amino acids.

Which amino acids contain a sulfur atom?

Sulfur is a component of the following sulfur-containing amino acids:

Cysteine (Cys) — side chain $-CH_2SH$, contains a thiol/sulfhydryl group.
Methionine (Met) — side chain $-CH_2CH_2SCH_3$, contains a thioether group.
Cystine — formed by disulfide bonds linking two cysteine residues together.

What state are the functional groups of amino acids in within the body?

Under physiological conditions, they are ionized: the $\alpha$-amino group becomes a cation ($-NH_3^+$), and the $\alpha$-carboxyl group becomes an anion ($-COO^-$).

What is the peptide backbone?

It is the central axis of a polypeptide chain consisting of repeating $-NH-CH-CO-$ chemical groups, to which side chains are attached.

Why is proline considered an exception among amino acids?

Because it is an imino acid. Its side chain forms a ring by bonding with the imino group, meaning the nitrogen atom in the resulting peptide bond lacks a hydrogen atom.

How do hydrophilic amino acids differ from hydrophobic ones?

Hydrophilic amino acids have anionic, cationic, or polar groups in their side chains and are capable of hydration. Hydrophobic ones contain nonpolar hydrocarbon chains or rings and avoid water.

Go deeper

Mechanisms of genetic determination of amino acid sequences in DNA
Correlation between phenotypic traits and the structure of specific proteins
Impact of amino acid substitutions on the development of hereditary diseases
Spatial organization of the peptide backbone and formation of protein structures