Bioactive solution structure of the gastrointestinal polypeptide GIP with active regions in red and blue
A team of researchers led by Professor Paul Malthouse, principal investigator with the Centre for Synthesis and Chemical Biology and UCD Conway Institute, uses state-of-the art NMR equipment to study a range of biological processes. Insights gained could help in the design of drugs for an array of medical conditions.
NMR spectroscopy is unravelling the secrets of previously inaccessible biological macromolecules, thanks to recent advances in the field. Bigger and more powerful spectrometers with higher magnetic field strengths offer new insights into the reactions happening in our bodies.
Protein-digesting enzymes called proteases play a role in propagating the AIDS virus, in allowing cancers and parasites to move through tissues and they also play a part in the production of the plaque protein which causes Alzheimer’s disease. Inhibiting these enzymes is key to treating such diseases.
“We are synthesising protease inhibitors and using NMR to determine how they interact with specific proteases. By studying these interactions we hope to see ways of optimising an inhibitor’s ability to inhibit the specific protease involved in a given disease,” explains Professor Malthouse.
Professor Paul Malthouse and Dr Chandralal Hewage at the NMR centre in the UCD Conway Institute.
It is essential that potent protease inhibitors designed will only target the protease involved in the disease and not those which are essential for our bodies. “We are currently starting to synthesise and characterise a range of inhibitors which we hope will provide important insights into the development of drugs to treat a range of medical conditions,” continues Professor Malthouse.
A group including Professor Malthouse and Dr Chandralal Hewage, NMR scientist at the NMR Centre in UCD Conway Institute, have exploited NMR technology to solve the 3D solution structure of the gastrointestinal polypeptide GIP. GIP is a hormone that stimulates the secretion of insulin after ingestion of food.
A 3D picture of the protein was built step by step using a range of NMR experiments and molecular modelling calculations. Dr Hewage explains the significance of these studies: “Understanding the structural requirements for the biological activity of GIP will help in the design of new drugs for diabetes and obesity-related disorders.”
