Oxford: Chemical method for protein modification

Development opportunity

Oxford researchers Gonçalo Bernardes, Justin Chalker, James Errey and Ben G. Davis have developed a new method for the site-selective modification of proteins. This technology is the subject of an international patent application, and Oxford University’s technology transfer company, Isis Innovation, would like to talk to companies interested in developing the commercial opportunity that this represents.

Post-translational modification (PTM) is an important step in protein biosynthesis that increases the range of functions of a protein. Selective engineering of proteins using PTM has been used to develop proteins to treat cancer, cystic fibrosis, diabetes, anaemia, and more.

The market for therapeutic proteins is large – $37 billion in 2003 –  and is expected to reach $90 billion by 2010. But it is tricky to  bioprocessing therapeutic proteins accurately and consistently because they are sensitive to the conditions in which they are prepred.

This presents challenges for the manufacture, regulation and safety of therapeutic proteins – and an immediate need for methods that enable proteins to be modified in specific and controllable ways.

The Oxford researchers convert cysteine, a sulphur-containing amino acid, to dehydroalanine (Dha) via an oxidative elimination. Dha provides a convenient chemical handle for further post-translational modifications, enabling other molecules

(e.g. peptides, carbohydrates, lipids, phosphates) to be attached selectively to proteins. Polypeptides and glycoproteins, which have applications in synthetic vaccines and in cancer and haematological treatments, are just two examples of modified proteins that can be accessed using this method.