Thiol--Disulfide Interchange: Design, Synthesis, and Evaluation of Reagents and Organocatalysts for Chemical Biology

The redox state of sulfhydryl groups can have a profound effect on protein structure and function. In cells, this maintenance entails thiol-disulfide interchange reactions, which are often initiated by a membrane-associated protein, and then mediated by a soluble protein or peptide. In vitro , small-molecule thiols and disulfides, with finely tuned physicochemical properties, can accomplish this task. As a result, the development of reagents that modulate this essential chemistry is of great importance in the fields of chemistry and biology. Herein, the design, synthesis, and evaluation of organocatalysts that promote and mediate thiol-disulfide interchange chemistry are discussed, along with their uses in chemical biology.