A phosphine-based redox method for direct conjugation of disulfides.

Technologies for cysteine disulfide detection and conjugation are pivotal to understanding protein functions and developing disulfide-derived therapeutic agents. Currently, disulfide modification requires reductive cleavage prior to functionalization, posing challenges to differentiating disulfides from free thiols. We describe herein Redox-assisted Disulfide Direct Conjugation (RDDC) as a new method to enable disulfide rebridging without cross-reacting with free thiols.