Serine-Selective Bioconjugation

J Am Chem Soc. 2020 Oct 14;142(41):17236-17242. doi: 10.1021/jacs.0c05595. Epub 2020 Oct 5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Binding Sites
  • Models, Molecular
  • Oxidation-Reduction
  • Peptides / chemistry*
  • Phosphorothioate Oligonucleotides / chemistry
  • Phosphorylation
  • Protein Conformation
  • Serine / chemistry*
  • Ubiquitin / chemistry


  • Amino Acids
  • Peptides
  • Phosphorothioate Oligonucleotides
  • Ubiquitin
  • Serine