Electrochemical glycoprotein synthesis

We aim to develop selective and site-specific chemical modification reactions in the complex setting of synthetic and recombinant proteins using novel environmentally benign processes. Peptides and proteins tend to contain a distribution of several functional groups where specifically targeting a single site can be extremely challenging. However site selective peptide modification is an important feature of designed and engineered (bio)therapeutics, often dramatically improving therapeutic potential.
We intend to build peptides containing modifications, such as head-to-tail cyclisation or carbohydrate addition, using chemoselective chemical reactions (EPSRC areas: Synthetic Organic Chemistry, Chemical Biology and Biological Chemistry). However, these reactions often tend to leave a trace/"scar", resulting in unnatural and potentially immunogenic products, unless the chemical handles used to facilitate the process are removed. This can be done using selective (free radical) chemistry but often uses noxious reagents and processes which do not lend themselves to streamlining approaches including one-pot multi-step reaction sequences. We will explore the removal of the chemical handles using cleaner and more sustainable electrochemistry to generate the radical species (Electrochemical Sciences, Surface Science). This will be conducted in water as solvent, free from potentially explosive radical initiators, as well as stoichiometric toxic and expensive transition metals.
If successful, the results will be of much interest both academically and industrially in the growing biopharmaceutical market.