Site-selective protein modification with polymers for advanced biomedical applications

Protein modification with polymers has led to intriguing and new types of bioconjugates. They combine the tunable physicochemical properties of the polymers with the specific biological activity of the proteins. These unique attributes of protein-polymer conjugates render them interesting and useful in biomedicine. However, the application potential of protein-polymer conjugates is limited by the mostly non-selective protein modification with polymers due to the lack of site-selective protein modification technology. Recent advances in site-selective protein modification and controlled polymerization have made it possible to modify proteins with polymers in a site-selective and controlled manner. In this review, recent advances in site-selective protein modification with polymers are depicted in five parts as follows: site-selective protein modification; site-selective polymer modification; site-selective in situ growth of polymers from proteins; biosafety of polymers; and biomedical applications. Site-selective protein-polymer conjugates are superior to non-selective ones in precise control of structures and functions, which makes them more interesting for advanced biomedical applications ranging from protein delivery to diagnostics. Particularly, important examples in this regard are highlighted in this review. Additionally, major challenges and future directions in this emerging research field are also discussed in the perspective section of this review.