Inventing new reactions for chemical proteins synthesis

Proteins are the major component of cells and are essential for all living organisms: they are virtually involved in all biological functions. Access to pure form of a given protein is essential for modern medicine and life science. As a complement to biotechnological production (recombinant protein expression), the chemical synthesis of proteins has emerged as a viable approach to some protein targets and offers several advantages including the potential to incorporate any unnatural amino acid, post-translational modification, and also to conjugate drugs or probes. Another exciting aspect of chemical protein synthesis is the ability to prepare mirror-image proteins, which are increasingly finding applications in drug discovery and synthetic biology.

A critical concept is the use of chemoselective condensation reactions called “chemical ligation” which permit the assembly of a protein through unambiguous coupling of unprotected segments in aqueous solutions. One such reaction is “Native Chemical Ligation” (NCL) discovered 25 years ago. NCL has been a transformative advance in protein chemical synthesis, remains an unbeaten reaction, but is not ideal for many protein targets. To overcome the limitations of NCL, and to push beyond the boundaries of chemical protein synthesis, more general and complementary chemical ligation reactions are needed. For this purpose many laboratories including the host team are being vigorously pursuing toward this goal.

In this talk, I will give an overview of the history of chemical protein synthesis and chemical ligation reactions, and I will finish with my project outcome on a novel promising reaction.