Objective
In all multi-cellular organisms, oxygen homeostasis represents a fundamental physiological challenge and requires the co-ordinated regulation of an array of genes. Under hypoxic conditions levels of hypoxia inducible factor, a transcription factor, rise and enable transcription of an array of genes involved in the hypoxic response. Under nomadic conditions, levels of HIF are suppressed by the action of oxygen dependent hydroxyls. This project will contribute to the biochemical knowledge and medicinal exploitation of the hydroxyls (HIF PH), which have been recently established as key regulators of cellular oxygen sensing. Selective inhibitors not only for HIF PH in general, but also for tissue specific HIF PH is-enzymes will be designed and tested. Initially, analogues of 2-oxoglutarate for the HIF PH will be synthesised with the aim of mimicking enzyme/sub-co substrate complexes. X-ray crystallography, NMR, UV/vies, mass spectrometry and kinetics will study these complexes. The second phase will involve the design and testing of isohyets inhibitors and will involve a combination of binding to co substrate and substrate binding sites. A series of peptide and peptidomimetic libraries based on the modelled HIF: HIF hydroxyls interactions will be synthesised. By varying the LXXLAP binding motif of the substrate, it should be possible to obtain inhibitors selective towards HIF PH is forms. It is hoped that inhibitors of HIF PHs might be used to activate HIF and enhance angiogenesis in is chemic/ hypoxic disease. Therapeutic possibilities include the induction pro-angiogenesis via HIF PH inhibitors as an alternative to heart by-pass surgery and that inhibitors may be used as a treatment for treatment of anaemia, providing an alternative for the use of expensive recombinant erythropoietin protein. The Oxford group has recently solved the crystal structure of HIF hydroxyls.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering crystals
- medical and health sciences clinical medicine surgery
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences chemical sciences analytical chemistry mass spectrometry
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-5
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
OXFORD
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.