The attachment of synthetic molecules to proteins with desired structure and function allows for the formation of hybrid materials that can capitalize on the properties of both components. The utility of these bioconjugates has been realized in a variety of contexts, such as cellular imaging, light harvesting, drug delivery, water remediation and tissue engineering. Traditional methods used in protein modification target the side chains of native amino acid residues, such as lysines and cysteines. However, depending on the relative abundance of these residues on the solvent exposed protein surface, it can be difficult to target them in a controlled and site-specific manner while maintaining native protein function. As a result, many newer techniques for protein modification target uniquely reactive sites, such as C-terminal thioesters, N-terminal groups, artificial amino acids, and specific recognition sequences for enzymatic ligations. Each of these new methods has expanded the scope of bioconjugates that can be accessed, and the applications of well-defined bioconjugates are proceeding apace.
Toward these efforts, we strive to expand the bioconjugation toolbox through the development of new site-selective protein modification methods that offer mild reaction conditions. We have worked out the chemistry for several reactions, which target sites such as the N-terminus of a protein, and even aniline moieties that can be engineered onto a protein and coupled to aminophenols via oxidative coupling. To this end, we are continually striving to expand the current methods as well as explore newer approaches for site-selective protein modification within our lab.