Fast and Selective Cysteine Conjugation Using para-Quinone Methides

An efficient and selective method for cysteine conjugation utilizing para-quinone methides (p-QMs) was developed. p-QM labeling exhibits high specificity toward the cysteine residue, as evidenced by its reactivity with various amino acid derivatives, peptides, and proteins. Notably, the p-QM-cysteine reactions display robust kinetics with rate constants up to 1.67 × 10⁴ M^-1·s^-1. Furthermore, p-QM conjugation enables us to attach a fluorescent probe to a HER2 nanobody, resulting in selective labeling of HER2-positive SK-BR-3 cells.