Objective
The emergence of multi-drug resistant pathogens is a serious global problem. In this alarming situation, novel targets for which inhibitors with an unprecedented mode of action can be developed are urgently required. This proposal aims at the development of selective and potent inhibitors of the important and underexplored anti-infective target DXS, an enzyme from the 2C-methyl-D-erythritol 4-phosphate pathway that is entirely absent in humans but is essential for medically relevant pathogens (e.g. Plasmodium falciparum, Mycobacterium tuberculosis, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus). Despite substantial efforts dedicated to the discovery of inhibitors for DXS, to date very few active compounds have been reported and none of them fulfil the requirements as an ideal candidate for further development. To address these issues and maximise the chances of success, we will use dynamic combinatorial chemistry (DCC) as a hit identification strategy for the first time for the enzyme-DXS. To explore hitherto unexplored parts of the chemical space, we will pioneer the use of chiral heterocyclic building blocks in DCC for the discovery of potent inhibitors of the enzyme DXS. Use of chiral heterocycles in DCC will allow to rapidly access novel scaffolds. These chiral heterocyclic scaffolds will be evaluated for their biochemical activity on bacterial DXS. The most promising candidates will be tested in in vivo cell-based assays in bacteria.
The proposed approach for the design of chiral heterocyclic inhibitors for novel targets such as the enzyme DXS will enhance the knowledge about this underexplored target and will open up access to various potent inhibitors. Hence, this research programme will greatly improve the chances of idnetifiying new anti-infective agents with a novel mode of action, leading to socio-economical benefits for the health care sector in the European Union and also globally.
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 microbiology bacteriology
- natural sciences chemical sciences organic chemistry heterocyclic compounds
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance multidrug resistance
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF-EF-ST - Standard EF
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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.
(opens in new window) H2020-MSCA-IF-2017
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
38124 Braunschweig
Germany
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.