Peptide bond

A peptide bond forms when the carboxyl group of one amino acid condenses with the amine group of the next, releasing a molecule of water. The result is an amide linkage that is rigid and planar, which is part of why peptide chains adopt the shapes they do. Making these bonds one at a time in a controlled order is what solid-phase peptide synthesis does, and the yield and purity of that process are what a certificate of analysis reports.

Breaking peptide bonds is how the body clears peptides. Enzymes called proteases and peptidases cut the chain at specific residues, and the speed at which they do so sets a peptide's half-life. A native GLP-1 molecule lasts a couple of minutes in blood because the enzyme DPP-4 cuts it near one end. Semaglutide lasts a week because that position was modified so the enzyme cannot act, and a fatty-acid chain was added so the peptide binds albumin.

The same vulnerability explains oral bioavailability. Most peptides are cut to pieces in the stomach and small intestine before absorption, which is why the research literature uses injection for nearly all of the compounds profiled here and why BPC-157, which survives gastric juice, is an exception worth noting.