Protein Modification: Strengthening the Bond - Isis Project No 3433

Oxford researchers have developed a method for converting disulfide- to thioether-linked glycoconjugates, which can be used to prepare glycoproteins with enhanced chemical and enzymatic stability.

Marketing Opportunity

The use of proteins as drugs is well established. In 2003, therapeutic proteins produced revenues over £37bn. There is considerable scope to increase the use of protein-based drugs and scientists are exploring methods for controlling the in vivo behaviour of proteins. Mimicking nature’s use of carbohydrates to control the way that proteins are transported, recognised by tissues, absorbed by cells, and metabolised has proved very successful. Erythropoietin (EPO), a glycoprotein hormone which controls red blood cell production, is currently the most successful protein-based drug with a 25% share of the therapeutic protein market ($10.7bn, 2005). Protein therapeutics is a young field and much remains to be understood about the relationship between protein structure and function. New methods that enable specific and controllable glycosylation of proteins would facilitate the development of new protein-based drugs.

The Oxford Invention

Oxford researchers have developed a new method for the preparation of thioether-linked glycoproteins from disulphide-linked precursors.¹

A readily available chemical reagent (tertiary phosphine) mediates contraction of disulphide (RS-SR', R = protein, R' = carbohydrate) bonds in glycopeptides and glycoproteins to provide the corresponding thioether-linked (R-SR') glycoconjugate in high yields. The resulting glycoproteins exhibit enhanced chemical and enzymatic stability. Such glycoproteins offer numerous advantages for therapeutic applications, including extended in vivo circulatory lifetimes, more selective delivery to target cells, and enhanced therapeutic efficacy.

 

Ref 1. G.J.L. Bernardes, E.J. Grayson, S. Thompson, J.M. Chalker, J.C. Errey, F. E. Oualid, T.D.W. Claridge, B.G. Davis, Angew. Chem. Int. Ed. 2008, 47, 2244-2247.

Patent Status

This technology is the subject of an international patent application, and Isis would like to talk to companies interested in developing the commercial opportunity that this represents.

Request Further Information: Project Number 3433 - Protein Modification: Strengthening the Bond