The breaking down of proteins and peptides into smaller pieces—the reason injectable peptides don’t last long in your body.Proteolysis is the hydrolytic cleavage of peptide bonds, catalyzed by proteases/peptidases. For therapeutic peptides, proteolysis is the dominant elimination pathway determining plasma half-life. Proteolytic degradation occurs in plasma (by circulating proteases), at injection sites (by tissue peptidases), in the liver (first-pass metabolism for oral peptides), and at target tissues. Resistance to proteolysis is the central pharmacokinetic challenge in peptide drug design—addressed through chemical modifications including D-amino acid substitution, cyclization, PEGylation, and fatty acid conjugation.R↑ Top