Abstract

Genetic code expansion enables site-specific incorporation of designer amino acids into proteins produced in cells and animals. Recent innovations in the efficiency of unnatural amino acid incorporation is enabling researchers to study the function and regulation of cellular proteins with extraordinary molecular level insights being achieved. Our chemical genetic approach will be discussed that utilizes expanded genetic code techniques to direct small molecule ligands to a single protein of interest. Incorporation of an unnatural amino acid into a disease-causing protein enables for the rapid visualization or inducible control of the protein. Current research efforts will be shared that utilize the unique biorthogonal reactivity between the unnantural amino acid and small molecules to drive rapid, potent, and selective kinase inhibition in cells. The ability to selectively and rapidly interrogate the function of single proteins in healthy and disease cells is a central role in efforts to develop new personalized medicines.