Serine-Selective Bioconjugation

Abstract

The first general method for the rapid, chemoselective, and modular functionalization of serine residues in native polypeptides is reported using a reagent platform based on P(V) oxidation state. This redox-economic approach can be used to append nearly any kind of cargo onto serine, generating a stable, benign, and hydrophilic phosphorothioate linkage. The method tolerates all other known nucleophilic functional groups of naturally occurring proteinogenic amino acids. A variety of applications can be envisaged by this expansion of the toolbox of site-selective bioconjugation methods.