Serine-Selective Bioconjugation
Julien C. Vantourout, Srinivasa Rao Adusumalli, Kyle W. Knouse, Dillon T. Flood, Antonio Ramı́rez, Natalia M. Padial, Alena Istrate, Katarzyna Maziarz, Justine N. deGruyter, Rohan R. Merchant, Jennifer X. Qiao, Michael A. Schmidt, Michael J. Deery, Martin D. Eastgate, Philip E. Dawson, Gonçalo J. L. Bernardes, Phil S. Baran
Abstract
This Communication reports the first general method for rapid, chemoselective, and modular functionalization of serine residues in native polypeptides, which uses a reagent platform based on the P(V) oxidation state. This redox-economical 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.