Modification of N-Terminal α-Amine of Proteins via Biomimetic ortho-quinone-mediated Oxidation

Naturally abundant quinones are important molecules, which play essential roles in various biological processes due to their reduction potential. In contrast to their universality, the reactions between quinones and proteins remain sparse. Herein, we report the development of unprecedented strategy to protein modification via a biomimetic quinone-mediated oxidation at the N-terminus. By exploiting unique reactivity of an ortho-quinone reagent, the α-amine of protein N-terminus was oxidized to generate aldo or keto handle for orthogonal conjugation. Its applications have been demonstrated using a range of proteins, including myoglobin and ubiquitin. The effect of this method was further highlighted via the preparation of a series of 17 MIP-1β analogs, followed by preliminary anti-HIV activity and cell viability assays, respectively. This method offers a fast, efficient and complementary approach to existing strategies for protein N-terminus modification.