What Is a Peptide Bond?

A peptide bond is the covalent chemical linkage that joins two amino acids together. It is formed when the carboxyl group of one amino acid reacts with the amino group of another. During this process, a water molecule is released in what is known as a condensation reaction. The resulting structure is a CO–NH bond, also referred to as an amide linkage.

How Peptide Bonds Form

For a peptide bond to form, the participating amino acids must align so that the carboxylic acid group of one can react with the amine group of another. This process results in the creation of a dipeptide (two amino acids connected), which is the simplest form of peptide.

As more amino acids are linked, longer chains develop:

• Peptides: generally fewer than 50 amino acids
• Polypeptides: around 50–100 amino acids
• Proteins: typically more than 100 amino acids

Hydrolysis, or the chemical breakdown of a compound by reaction with water, can reverse this process by breaking peptide bonds. Though hydrolysis occurs slowly on its own, peptide bonds are considered metastable, meaning they can be broken down under certain conditions. The reaction releases about 10 kJ/mol of energy, and peptide bonds absorb light in the 190–230 nm range.

In biological systems, specialized enzymes are responsible for both the creation and cleavage of peptide bonds. This makes peptides and proteins central to processes involving hormones, neurotransmitters, antibiotics, and many signaling molecules studied in research.

The Structure of the Peptide Bond

Structural studies, particularly those using x-ray diffraction, have shown that peptide bonds are inherently rigid and planar. This rigidity is due to resonance stabilization, where the nitrogen atom of the amide group delocalizes its lone pair of electrons toward the carbonyl oxygen. This resonance creates partial double-bond character in the N–C bond, restricting rotation around the bond axis.

Key structural features include:

• The N–C bond in the peptide linkage is shorter than a standard single bond.
• The C=O bond is slightly longer than typical carbonyl bonds due to electron delocalization.
• The carbonyl oxygen and the amide hydrogen adopt a trans configuration (opposite sides), which is energetically more favorable than cis due to reduced steric hindrance.

The Polarity of Peptide Bonds

Because of resonance, peptide bonds have approximately 40% double-bond character, making them partially rigid rather than freely rotatable. This resonance also gives the bond a permanent dipole moment: the oxygen carries a partial negative charge (–0.28), while the nitrogen carries a partial positive charge (+0.28).

This polarity is critical for the stability and folding of peptides and proteins, influencing how chains interact with each other and with surrounding molecules. The restricted rotation and dipole moment help define the secondary and tertiary structures of larger proteins.