Objective
The development of potent, selective and cell-permeable small molecule chemical probes as tools to interrogate and modulate cellular functions of the human proteome is a rapidly growing field. The direct manipulation of protein intracellular level and activity using small molecules has enormous potential to elucidate and validate new drug targets and therapeutics tools. In the last decade, researchers have discovered an alternative method to directly control the level of protein components inside the cell without altering its DNA or RNA. This approach uses chemicals known as PROteolysis TArgeting Chimeric moleculeS (PROTACS) which exploit the ubiquitin/proteasome pathway to direct the intracellular degradation of any Proteins Of Interest (POI) by linking a section that mimics the recognition? motif of the natural substrate to one that binds the POI. PROTACS enable recruitment of any POI to an E3 Ubiquitin ligase. To date, the strategy has displayed some success, however much improvement is still required to known compounds to make this approach widely useful, and althernative new strategies need to be developed to add to the current arsenal of chemical tools.
In preliminary work leading to this proposal the Ciulli Lab. (University of Cambridge) has discovered and characterised the first drug-like small molecules that target the Von Hippel Lindau (VHL) E3 Ubiquitin Ligase and disrupt its interaction with substrate Hypoxia Inducible Factor (HIF) with low micromolar affinities. Harnessing this knowledge, and using these inhibitors as starting points, the proposed research will develop a multidisciplinary approach combining medicinal chemistry, protein engineering with biophysical studies and concerning designed, mutated/engineered VHL-ligand pairs that could ultimately be exploited as an orthogonal approach to modulate the level of any protein inside the cell.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences basic medicine medicinal chemistry
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics RNA
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Programme(s)
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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.
FP7-PEOPLE-2012-IEF
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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
DD1 4HN Dundee
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.