Abstract:
Proteins are the most abundant biomolecules within a cell and are involved in all biochemical cellular processes, fulfilling specific functions with unmatched precision. This unique specificity makes proteins an ideal scaffold to generate tools for the exploration of natural systems or for the construction of modern therapeutics. Thus, the chemoselective modification of proteins with functionalities that are not defined by the genetic code has become an indispensable approach for life science research and the development of therapeutics. Amongst site-selective strategies for protein modification, cysteine-selective approaches have long been used for the generation of functional protein conjugates and new reactions continue to emerge, offering solutions for diverse research questions. In this review, we are highlighting new strategies for the chemoselective modification of cysteine residues in peptides, proteins and antibodies with a particular focus on the most recent years. We lay special focus on new reagents for efficient cysteine conjugation that produce stable conjugation products with significant pharmaceutical application.