Site-specific chemical modifications of proteins

Since long, peptides and proteins have been recognized as targets for the development of synthetic methodologies. There have been major advances in the development of methods for the site-specific modifications. The naturally occurring functionalities in peptides and proteins are used to modify the less common amino acid targets. The most important benefit of chemical bioconjugation techniques using naturally occurring amino acids is that they do not require additional biochemical techniques to install unnatural functionalities for chemoselective reactions. However, unnatural functionalities can well be incorporated into peptides and proteins followed by the establishment of bioorthogonal coupling methodologies. The unnatural amino acids can be incorporated into proteins either in a site-directed or residue-specific fashion. Bioorthogonal chemistry is an important tool for the development of synthetic methodologies and for further advances in biological research. A variety of methods exist that tag cellular components with reporters not only for visualization but also for isolation from biological samples. In this review, we present an overview of the efforts of both chemical and biochemical approaches to functionalize peptides and proteins with the desired molecular components. We focus on the site-directed methods to incorporate unnatural groups into biomolecules and the development of bioorthogonal transformations involving unnatural functional groups.