Enzymes called peptidases, present in the blood and tissues, break peptides down quickly, and most peptides are poorly absorbed from the gut. Reviews of peptide pharmacokinetics — the study of how the body absorbs and clears a compound — report half-lives measured in minutes for many of the body’s own signalling peptides, meaning half of what is present is broken down in that short time.
Almost every structural change you will meet in this field is an answer to that problem: swapped-in amino acids that enzymes cannot cut, fatty-acid chains that make the peptide cling to albumin (a carrier protein in the blood), and joining the two ends into a ring to stiffen the molecule. Understanding a modified version usually means understanding which breakdown route it was designed to survive.
