Scientific Glossary

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Proteases are ubiquitous: in digestive secretions (pepsin, trypsin, chymotrypsin), in blood (DPP-4, NEP, ACE), and intracellularly. Most therapeutic peptides are rapidly cleaved by proteases, limiting their half-life and restricting delivery to injectable routes. Semaglutide overcomes this through C-18 fatty acid conjugation (albumin binding) and selective amino acid modifications. Research strategies to resist proteolysis include: D-amino acid substitution, PEGylation, cyclization, and N-terminal acetylation. Understanding proteolytic stability is essential for interpreting peptide pharmacokinetic data.