Late-Stage Modification of Polypeptides through One-Step Biocompatible Electrochemical Sulfation

Tyrosine sulfation is an important post-translational modification (PTM) that directs sulfate groups to tyrosine residues, resulting in sulfated proteins that provide essential cellular signalling process in living organisms, such as protein synthesis, cell division, metabolism, cell growth, signal transduction, and cell development. In this paper, we demonstrate that one-step electrochemical phenol and tyrosine sulfation can be performed in biological buffer solution without addition of an external chemical oxidant under ambient conditions powered by renewable energy. This atom-efficient electrochemical reaction is specific towards tyrosine residue instead of other amino acids and can be applicable toward exemplary dipeptides and biological active polypeptides. We envision this new green technology can enable late-stage electrochemical sulfation of polypeptides, proteins, and pharmaceuticals for proteomics, protein labelling, and therapeutic applications in the future.