The Chemical Methods of Disulfide Bond Formation and Their Applications to Drug Conjugates

: The disulfide bond possesses unique chemical and biophysical properties which distinguish it as one of the key structural elements of bioactive proteins and peptides, important drugs and other materials. The chemo-selective synthesis of these structures and the exploration of their function have been of longstanding interest to the chemistry community. The past decades have witnessed significant progress in both areas. This review will summarize the historically established and recently developed chemical methods in disulfide bond formation. The discussion will also be extended to the use of the disulfide linkers in small molecules, and peptide- and protein-drug conjugates. It is hoped that the combined overview of the fundamental chemistries and applications to drug discovery will inspire creative thinking and stimulate future novel uses of these versatile chemistries.