Exopeptidase
A protease enzyme that removes amino acids sequentially from either end of a peptide chain — aminopeptidases from the N-terminus and carboxypeptidases from the C-terminus. N-terminal acetylation and C-terminal amidation are common peptide modifications designed to resist exopeptidase degradation.
Technical Context
Aminopeptidases remove amino acids from the N-terminus (aminopeptidase N, leucine aminopeptidase) while carboxypeptidases remove them from the C-terminus (carboxypeptidase A, B, E). DPP-4 is technically an exopeptidase — it removes a dipeptide from the N-terminus. Terminal modifications (N-acetylation blocks aminopeptidases; C-amidation blocks carboxypeptidases; Aib at position 2 blocks DPP-4) are the most straightforward protective strategies. Cyclic peptides inherently lack susceptible termini. The relative contribution of exopeptidase vs endopeptidase degradation varies by peptide and determines which stabilisation strategy is most effective.