Going Non‐native To Improve Oxidative Protein Folding

Chemical origami: Protein folding rates and yields can be limited by the presence of kinetic traps. By replacing two cysteines with selenocysteines in bovine pancreatic trypsin inhibitor, Hilvert and co-workers increased the folding rate and removed two traps from the oxidative-folding pathway, even though the resulting diselenide would correspond to a non-native disulfide bond.