Current state of research

The ability to change amino acid sequences of proteins in a defined way is of high importance for today’s life science research. The revolutionary establishment of methods for the site-directed mutagenesis of DNA allows scientists to study and manipulate protein function on a whole new level. However, in the recent past these molecular methods reached their limits, caused by the restricted chemistry of the twenty proteinogenic amino acids. In order to fully understand protein function and systematically use this knowledge for biotechnological applications, chemical tools that exceed the diversity of the canonical amino acids are needed.

Posttranslational protein modifications like glycosylation or phosphorylation are nature’s way to extend the chemistry of its proteins.1 Such modifications play an important role for the regulation of many biological processes like signal transduction, protein-protein interactions or protein folding and stability.2 Dysfunctions in the biosynthesis of these posttranslational modifications are associated with many diseases including carcinogenesis or diabetes.  

Performing proteomic and functional studies with such modified proteins and thereby fully understanding the influence and exact role of protein modifications within biological systems remains a highly challenging target for live science research. The synthesis of posttranslationally modified proteins stretches molecular biology to its limits and homogenous mixtures make the isolation from natural sources extremely costly and work-intensive. Moreover, the fact that most of the enzymes that install these modifications and the proteins that subsequently interact with them are unknown, complicates the research on these biomolecules tremendously.3

The use of chemical methods to replicate modified proteins is one promising way to help address these challenges which gained a lot of attention within recent years. With the help of chemical tools, scientists were able to advance proteome analysis and allowed the localization and functional studies of post- and cotranslationally modified proteins.4