Disulfidelinked

Disulfidelinked or disulfide-linked refers to a molecular connection formed by a disulfide bond, a covalent linkage between two sulfur atoms, typically derived from thiol groups (R-SH) that are oxidized to form R-S-S-R'. In biological systems this often involves cysteine residues, and can be intramolecular (within a single molecule) or intermolecular (between two molecules).

Formation and cleavage: Disulfide bonds form through oxidation, often in the endoplasmic reticulum in proteins, facilitated by enzymes such as protein disulfide isomerase. Conversely, disulfide bonds can be cleaved (reduced) by reducing agents such as glutathione or thioredoxin in cells, or by chemical/enzymatic methods in the lab. In synthetic chemistry, disulfide bonds are formed by oxidation of thiol groups and can be subjected to disulfide exchange under reducing conditions, enabling reversible linking.

Biological and technological significance: Disulfide bonds stabilize protein structure, particularly extracellular and secreted proteins, contributing to folding and resistance to denaturation. The dimer cystine is the oxidized form of two cysteine residues linked by a disulfide. In biotechnology and medicine, disulfide linkers are used for cleavable bioconjugates such as some antibody-drug conjugates and prodrugs, allowing payload release in reducing intracellular environments. In materials science, disulfide linkages serve in smart polymers and nanoparticles as reversible crosslinks.