A Peptide-Based Ligand-Directed Chemistry Enables Protein Functionalization
Yuena Wang, Rongtong Zhao, Chuan Wan, Xiaochun Guo, Fenfang Yang, Zhanfeng Hou, Rui Wang, Shuiming Li, Tiejian Feng, Feng Yin, Zigang Li
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.
Topics & Concepts
ChemistrySulfoniumThioetherCysteineLigand (biochemistry)PeptideCombinatorial chemistryProtein ligandStereochemistryBiochemistryEnzymeOrganic chemistryReceptorSalt (chemistry)Click Chemistry and ApplicationsChemical Synthesis and AnalysisBiotin and Related Studies