N-terminus

Meaning: The N-terminus is the end of a peptide chain where the first residue still has its free α-amino group, –NH₂ or –NH₃⁺ at physiological pH. The opposite end, the C-terminus, keeps a free α-carboxyl group. A peptide bond joins the carboxyl of one residue to the amino group of the next, so the backbone amines and carboxyls in the interior are all tied up as amides. Only the two ends keep free α-groups.

Sequences are written, numbered and named starting at the N-terminus. In Ala-Gly-Ser, Ala is the N-terminal residue and Ser is the C-terminal residue. In translation, the chain grows from the N-terminus toward the C-terminus.

On the MCAT: You may be asked to identify the N-terminal residue, draw a short peptide in the correct direction, or find the charge of a peptide at a given pH. The N-terminal amine has a pKa near 9 and the C-terminal carboxyl near 2. At pH 7 the ends are therefore –NH₃⁺ and –COO⁻. Titration curves of peptides combine these two groups with any ionizable side chains.

Common confusion: The N-terminus is only the α-amino group at the start of the backbone. A side-chain amine, such as the one on lysine, is not an N-terminus, even if it is protonated. Reversing the direction of a drawn peptide also changes which residue is N-terminal, so check which end holds the free amine.