Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan

Org Lett. 2023 Jul 28;25(29):5459-5464. doi: 10.1021/acs.orglett.3c01795. Epub 2023 Jul 18.


Across eukaryotic proteomes, tryptophan is the least abundant of the 20 canonical amino acids, which makes it an ideal chemical handle for the late-stage functionalization of peptide and protein scaffolds with minimal production of undesired isoforms. Herein, we report the photocatalytic C2-alkylation of tryptophan using bromodifluoroacetate/acetamide-derived radical precursors. This rapid visible-light-mediated reaction is additive-free, operationally simple, and tolerates diverse functionality. We demonstrate the late-stage modification of a variety of complex peptides, including examples of biological significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Amino Acids / chemistry
  • Peptides* / chemistry
  • Proteins / chemistry
  • Tryptophan* / chemistry


  • Tryptophan
  • Peptides
  • Proteins
  • Amino Acids