Disulfide bridge

Two cysteine amino acids can link through their sulfur atoms to form a disulfide bridge, a covalent bond that pins two parts of a peptide chain together. In a small peptide the bridge often makes the difference between a floppy chain and a defined loop that fits its receptor. It is formed as the final step of synthesis by controlled oxidation, and it must survive storage and handling for the peptide to work.

Several compounds profiled here depend on one. AOD-9604 and HGH Fragment 176-191 carry a bridge between two cysteines that mirrors the one in the parent growth hormone. Melanotan II and PT-141 are cyclic peptides closed by a lactam rather than a disulfide, a related strategy for the same goal. BPC-157, by contrast, has no cysteine and no bridge, which is one reason it tolerates harsh conditions.

A certificate of analysis confirms a bridge indirectly: the mass spectrometry result for a bridged peptide is two mass units below the linear sequence, because two hydrogens leave when the bond forms. Reducing agents and prolonged oxidative stress can break or scramble bridges, which is one more reason for careful cold-chain storage.