A Peptide-Based Ligand-Directed Chemistry Enables Protein Functionalization

Org Lett. 2022 Oct 7;24(39):7205-7209. doi: 10.1021/acs.orglett.2c02974. Epub 2022 Sep 28.

Abstract

The ligand-directed (LD) chemistry provides powerful tools for site-specific modification of proteins. We utilized a peptide with an appended methionine (Met) as a ligand; then, the Met thioether was modified into sulfonium which enabled a proximity induced group transfer onto protein cysteine in the vicinity upon peptide-target binding. The sulfonium warhead could be easily constructed with unprotected peptides, and the transferable group scope was conducted on model protein PDZ and its ligand peptides. In addition, a living cell labeling was successfully achieved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cysteine*
  • Ligands
  • Methionine
  • Peptides* / metabolism
  • Proteins
  • Sulfides

Substances

  • Ligands
  • Peptides
  • Proteins
  • Sulfides
  • Methionine
  • Cysteine