Protein-Protein Interaction in Multicomponent Reaction Enables Chemoselective, Site-Selective, and Modular Labeling of Native Proteins

A protein's pool of functionalities presents aformidablechallenge for its single-site modification. Here, we report a methodto harness protein-protein interaction (PPI) to drive selectivemodification. It involves the chemoselective reversible generationof reactive intermediates and utilizes PPI-specificity to drive thesubsequent site-selective irreversible step. The disintegrate (DIN) theory-driven multicomponent aza-Morita-Baylis-Hillman(aza-MBH) reaction offers homogeneous and modular single-site proteinmodification capable of late-stage mono- and dual-probe installation.

Automated summary

The method utilizes protein-protein interaction to selectively modify a protein through chemoselective reversible generation of reactive intermediates and subsequent site-specific irreversible step, providing a homogeneous and modular approach for protein modification.