A peptide bond is the amide linkage that joins amino-acid residues in a polypeptide. Formally, it can be represented as forming between the carboxyl group of one amino acid and the amino group of another with loss of water:

$$\mathrm{-COOH+H_2N-\rightarrow -CO-NH-+H_2O}.$$

The amino acids incorporated into the chain are then called residues because each has become part of the larger molecule.

A short chain of residues is a peptide; a longer chain is a polypeptide. Proteins consist of one or more polypeptide chains, often together with additional non-protein components.

Directionality

A polypeptide backbone has two chemically different ends:

• the N-terminus has the free or terminal amino-group end;
• the C-terminus has the free or terminal carboxyl-group end.

Protein sequences are conventionally written from N-terminus to C-terminus.

For a tripeptide with residues Ala-Gly-Ser, the order

$$\mathrm{Ala-Gly-Ser}$$

is not interchangeable with

$$\mathrm{Ser-Gly-Ala}.$$

They contain the same amino-acid composition but have different primary sequences because direction and connectivity differ.

The peptide bond is unusually rigid

The lone pair on peptide nitrogen can delocalize into the neighboring carbonyl group. Resonance therefore gives the C-N bond partial double-bond character. The atoms around the peptide linkage tend to remain approximately planar, and rotation around the peptide C-N bond is strongly restricted.

The backbone still has conformational freedom because rotation can occur around neighboring single bonds attached to the α carbon. Protein folding therefore comes mainly from allowed rotations around those bonds rather than free rotation through the peptide bond itself.

Peptide-bond hydrolysis reverses the connectivity and yields amino-group and carboxyl-group products. In water this cleavage is generally very slow without catalysis. Proteases are enzymes specialized for catalyzing peptide-bond hydrolysis.

The repeating backbone pattern

$$\mathrm{-N-C_\alpha-C(=O)-N-C_\alpha-C(=O)-}$$

provides a common structural scaffold, while the different side chains project from the α carbons and generate the chemical diversity of proteins.