How Do Amino Acids Join to Form a Polypeptide (Peptide Bond)?

Amino acids join by condensation reactions that form peptide bonds. Each bond forms between the carboxyl group of one amino acid and the amino group of another, with one molecule of water removed.

The Mechanism

This content is required at both SL and HL in IB Biology subtopic B1.2 Proteins.

1. Every amino acid has an amino group, $-\text{NH}_2$, and a carboxyl group, $-\text{COOH}$, attached to its central carbon atom.
2. The carboxyl group of one amino acid reacts with the amino group of another.
3. An $-\text{OH}$ is removed from the carboxyl group, while an $-\text{H}$ is removed from the amino group.
4. These atoms combine to form water, $\text{H}_2\text{O}$.
5. A covalent carbontonitrogen bond forms between the amino acids. The resulting $-\text{CO}-\text{NH}-$ linkage is the peptide bond.

The generalized reaction is:

$\text{H}_2\text{N}-\text{CH}(R)-\text{COOH} + \text{H}_2\text{N}-\text{CH}(R')-\text{COOH} \rightarrow \text{H}_2\text{N}-\text{CH}(R)-\text{CO}-\text{NH}-\text{CH}(R')-\text{COOH} + \text{H}_2\text{O}$

Two joined amino acids form a dipeptide. Repeated condensation reactions add more amino acids, producing a polypeptide. A linear chain containing $n$ amino acids has $n-1$ peptide bonds; for example, five amino acids form four peptide bonds and release four water molecules in the generalized condensation model.

Peptide bond formation links amino acids into a chain with an amino terminal end and a carboxyl terminal end. The R-groups do not form the backbone bond; instead, they project from the repeating backbone and determine the properties of the polypeptide. The reverse reaction is hydrolysis: water is added to break a peptide bond, separating the chain into shorter peptides or amino acids.

During translation, the ribosome catalyses successive peptide bond formation, extending the growing polypeptide according to the codon sequence of mRNA.

Exam Technique

For an IB “explain” question, identify the reacting amino and carboxyl groups, state that water is removed in condensation, and name the resulting peptide bond. A common misconception is that the bond forms between two R-groups; it forms between the carboxyl carbon of one amino acid and the amino nitrogen of the next.