Photo‐and Electrochemical Modification of Amino Acids, Peptides and Proteins through Cysteine: Recent Advances and Future Perspectives

Abstract

Chemical modification of peptides and proteins has emerged as an efficient strategy to study and manipulate the physical and chemical properties and biological functionalities of proteins. Among the 20 proteinogenic amino acids, cysteine is one of the most frequently targeted residues for chemical modification of peptides and proteins due to its unique thiol group and its relatively low natural abundance. Cysteine is able to partake in radical and atom‐, electron‐ and hydride‐transfer reactions taking the benefit of redox activity of thiol side chain. Recently, photo‐ and electrochemistry have emerged as influential methodologies for enabling novel transformations in organic synthesis. These two fields both involve the generation of radical intermediates through single electron transfer processes, which align well with the redox activity of cysteine residue. Furthermore, the mild and controllable features are suitable for solving the chemo‐ and regioselective problems of the existing bioconjugation strategies. Given the intrinsic benefits of photo‐ and electrochemical redox catalysis, the application of developing novel cysteine‐based bioconjugation methods is increasingly compelling. This review provides a comprehensive overview of recent advancements in photo‐ and electrochemical approaches for modifying cysteine amino acid residues, cysteine‐containing peptides, and proteins. The advantages of photo‐ and electrochemical redox catalysis and its applicability in developing novel biocompatible methods are discussed. Additionally, the current limitations of these methods and the challenges that need to be addressed in the future are also explored.