Disulfide bonds between cysteine residues help hold protein and peptide structures in place. As the number of cysteine residues increases, so does the number of ways they can form disulfide bridges. The resulting mixtures contain species of various activities, and isolating the desired form can be difficult. To simplify the complexity of such mixtures, Christian Heinis of ETH Lausanne and coworkers have developed dithiol amino acids (examples shown) that form two disulfide bonds at a single amino acid (Nat. Chem. 2014, DOI: 10.1038/nchem.2043). They used a serine protease inhibitor and a nicotinic acetylcholine receptor inhibitor as model systems. In each peptide, they replaced a pair of adjacent cysteines with one dithiol and an alanine. The resulting peptides have tertiary structures like those of their native counterparts. In addition, the dithiol-containing peptides bind their targets more strongly than the original peptides do. Symmetrically arranged dithiols eliminate the possibility of forming disulfide isomers and thus reduce mixture complexity. Heinis and coworkers plan to use the dithiols in the directed evolution of peptides and proteins.