Endopeptidase
A protease enzyme that cleaves peptide bonds within the interior of a peptide chain rather than at the ends. Key endopeptidases include trypsin, chymotrypsin, and pepsin. DPP-4, which degrades GLP-1, is technically an exopeptidase that cleaves near the N-terminus.
Technical Context
Major endopeptidases include the serine proteases trypsin (cleaves after Arg, Lys), chymotrypsin (cleaves after Phe, Trp, Tyr), and elastase (cleaves after small residues). In the bloodstream, neprilysin (EC 3.4.24.11) is a membrane-bound metalloendopeptidase that degrades numerous bioactive peptides. Pepsin in the stomach degrades peptides at low pH. Identifying the endopeptidase-susceptible sites in a therapeutic peptide sequence enables targeted modifications to improve stability. Cyclisation eliminates terminal cleavage sites but does not protect against endopeptidase cleavage within the ring — additional modifications may be needed at vulnerable internal positions.