A Peptide-Based Ligand-Directed Chemistry Enables Protein Functionalization

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.

Automated summary

The ligand-directed chemistry provides powerful tools for site-specific modification of proteins, and the use of sulfonium warhead enables group transfer. This method can be applied to model proteins and their ligand peptides, and successful cell labeling has been achieved.