Definition
A disulfide bridge forms when the thiol groups of two cysteine residues are oxidised to create a covalent S–S bond. Within a single chain it produces a loop; between chains it links them together, as in insulin, which has two interchain and one intrachain disulfide. Disulfides restrict conformational freedom and can improve resistance to proteolysis. Synthetic peptides with multiple cysteines require controlled oxidation, often using orthogonal cysteine protecting groups, to form the correct pairing, because mispaired isomers have the same mass. Oxytocin, vasopressin and octreotide each contain one disulfide. Reducing agents such as dithiothreitol break these bonds, so they should be kept out of solutions where the native structure matters.