Expanding the Genetic Code – Chemistry in Living Systems

 The desire to study and manipulate biological processes in their native environment has fuelled the development of approaches to endow proteins with new chemical groups in vivo. Genetic code expansion allows the site-specific incorporation of artificial, designer amino acids into virtually any protein in living cells and animals. Together with significant developments in designing and re-discovering chemistries that are amenable to physiological conditions and applicable in living systems (in vivo chemistries), these methods have begun to have a direct impact on studying biological processes.

An emerging area with enormous potential consists in the site-specific incorporation of unnatural amino acids with functional groups that allow subsequent covalent modification of the protein with biophysical probes and small molecules via chemoselective reactions. This provides an important approach for imaging protein location in live cells and can also be used for controlling enzyme’s activity in vivo. Likewise, the co-translational site-specific incorporation of unnatural amino acids bearing new functional groups that are inert under physiological conditions, but become reactive to form covalent linkages with biomolecules in their vicinity upon a certain trigger has become an important approach for understanding protein-protein interactions in live cells.

We envision that the approaches and technologies to expand the chemical repertoire of proteins by incorporating unnatural amino acids and developing new in vivo chemistries will enable the study of biological processes that are difficult or impossible to address by more classical methods.