Breakthrough
These new projects focus on proteins termed factor XI and factor XII (X-factors) that contribute to blood coagulation. Factor XI is the ‘newest’ X factor in evolutionary terms only occurring in mammals but not present in fish, amphibians, reptiles or even mammals that lay eggs (monotremes) such as the platypus.
Professor Jonas Emsley at The University of Nottingham’s
Centre for Biomolecular Sciences , has previously made a breakthrough by determining the molecular structures of factor XI and factor XII in studies funded by the British Heart Foundation.
Professor Emsley said: “Disease models of stroke have shown a significant role for activation of X factors which seem to be central to the pathology of the disease. Thus factor XII and factor XI are of great therapeutic interest in the drive to discover novel anticoagulant therapies to replace heparin and warfarin."
“These currently available treatments target multiple coagulation proteins which have a more central role in healthy blood clotting and hence are more prone to side effects such as bleeding.”
The groups of Professor Peter Fischer and Dr Lodewijk Dekker have expertise in drug discovery and have developed a platform for developing new medicines within the School of Pharmacy.
They use drug design methods based on high resolution structures determined using protein crystallography by the group of Jonas Emsley. They also make use of The University of Nottingham’s fully automated state-of-the-art Managed Chemical Compound Collection (MCCC) with more than 80,000 compounds for high through-put screening. This facility is key for identifying lead compounds capable of inhibiting the activity of coagulation factor XII.
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