Protein PEGylation is a technique routinely used to improve the pharmacological properties of injectable therapeutic proteins. PEG stands for polyethylene glycol, a synthetic polymer that is attached to proteins. The PEG chain artificially increases the size of the protein and improves its retention in the bloodstream. By remaining longer in the blood stream the protein therapeutic is more effective than normal.
Since PEGylation was developed in the 1970s, PEGylated proteins have significantly improved the treatment of several chronic diseases, including hepatitis C, leukemia, arthritis, and Crohn’s disease. PEGylated interferon is one of the most powerful therapeutics used to treat chronic hepatitis. Despite their importance the structure of PEGylated proteins has remained elusive. Now the first crystal structure of a protein modified with a single PEG chain has been determined through research at NUI Galway.
This important research was developed at NUI Galway by Italian PhD student Giada Cattani working with Dr. Peter Crowley, the lead author of the paper. The work also involved collaboration with Dr. Lutz Vogeley from the School of Biochemistry and Immunology at Trinity College Dublin and the crucial X-ray data was collected at the Diamond synchrotron in Oxford, UK.
Commenting on the research findings Dr. Peter Crowley from the School of Chemistry, NUI Galway commented, “The crystal structure reveals an extraordinary double helical arrangement of the protein! It is significant that this data was obtained at NUI Galway, the only Irish University to offer a degree programme in Biopharmaceutical Chemistry. This attractive programme provides training in an area that is essential for the development of new medicines and contributes to the Irish economy.”
A common approach to understand proteins is to crystallize them and determine their structure by using X-ray crystallography. This is necessary to understand what the protein looks like and how it functions. Thousands of research papers have been published about PEGylated proteins. Until the recent findings at NUI Galway there had been no success in crystallizing a PEGylated protein. The knowledge obtained by the Crowley lab has implications for understanding how PEGylated proteins work. The NUI Galway team is also looking at ways to engineer protein assemblies based on this result.