There are proteases in the blood, on cell surfaces, in the gut and inside cells. Some cut from the ends of the chain (exopeptidases: aminopeptidases at the N-terminus, carboxypeptidases at the C-terminus) and others cut inside it (endopeptidases), each at specific sequences.
Examples relevant to peptide research: DPP-4, which inactivates incretins and GHRH; neprilysin, which breaks down several vasoactive and natriuretic peptides; and trypsin, pepsin and chymotrypsin, which destroy peptides in the gut.
Almost all long-acting peptide engineering consists of dodging these enzymes: protecting the ends, replacing amino acids at cleavage sites, using D- or non-natural amino acids, cyclising the chain or hiding it bound to albumin.
Proteases explain why the oral route is so difficult for peptides and why biological samples used to measure them must be processed quickly or with inhibitors.
Related terms
Learn it in depth at the Peptide University
- Levels of structure and structure-activity relationship · Module 1
- Pharmacokinetics: ADME and parameters · Module 2
- Half-life engineering · Module 2
- Amylin, the oral route and the next generation · Module 3
- Non-injectable routes: intranasal, oral and topical · Module 8
Definition for educational and scientific purposes. It is not medical advice or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).