Biomimetic conjugation inspired from pheomelanin via thiol–quinone addition for enzymatic functionalization of fibroin

Fibroin has been extensively applied in the medicine, therapy, cosmetic, and food fields. Functional modification is a common route way to expand the application potential. Tyrosinase is versatile for enzymatic functionalization of fibroin by oxidizing tyrosine residues into dopaquinone. However, grafting of functional molecules to the protein-bound dopaquinone suffers from self-crosslinking due to competitive aryl coupling or addition with other nucleophile in protein. Herein, bioinspired from pheomelanin synthesis, a new approach with superior grafting efficiency and reaction rate for enzymatic grafting of protein was developed. The high reactivity of Michael addition between thiol and dopaquinone was utilized to promote the efficiency for grafting of PEG onto fibroin. The grafting of PEG with thiol group was superior to that with amine group. It demonstrated a superior efficacy for thiol group over amino group on enzymatic functionalization. This research firstly established an effective biomimetic approach for enzymatic functionalization of protein without the unexpected self-crosslinking. It could emerged to serve as the strategy of protein functionalization.