Objective
- To develop novel, potent and specific analogues of polyamine amides and polymethylene tetraamines containing aromatic units.
- To study the interactions of polyamine amides and polymethylene tetraamines with native and cloned acetylcholine and glutamate receptors
- To develop polyamines and polymethylene tetraamines as neuroprotectants.
The project is designed to develop novel, potent analogues of natural neuroactive amines occurring in wasp and spider toxins; these polyamine amides and polymethylene tetra amines containing aromatic groups are of interest as tools for investigating specific neuroreceptors in the central and peripheral nervous system. More importantly, the compounds are potential neuroprotectants for exploitation by the EU pharmaceutical industry. The project will involve close collaboration between medicinal chemists, pharmacologists, molecular biologists, neuropathologists and biochemists to achieve a set of carefully designed goals. The studies will target nicotinic and muscarinic acetylcholine receptors and ionotropic glutamate receptors, and will employ native receptors, in vivo and in vitro, as well as cloned receptors. Antagonism of these receptors by polyamine amides and polymethylene tetraamines will be optimised using biological evaluation as well as physico-chemical and structural characteristics of the compounds. The latter will involve NMR spectroscopy and molecular modelling. The biological optimisation will include receptor binding characteristics and electrophysiology.
Binding domains for the polyamines will be elucidated using photoaffinity labelling, receptor isolation and purification and peptide sequencing. The potential binding domains will be evaluated using cloned receptors mutated at single or multiple sites. A strong synthetic chemistry programme will underpin the biological investigations and provide a series of systematically designed novel compounds with pharmaceutic potential. Selected polyamine amides and polymethylene tetraamines emanating from these studies will be synthesised in quantity and evaluated in whole animal assays for their neuroprotective properties.
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 neurobiology
- natural sciences biological sciences biochemistry biomolecules
- natural sciences physical sciences optics spectroscopy absorption spectroscopy
- natural sciences chemical sciences organic chemistry amines
- medical and health sciences basic medicine pharmacology and pharmacy
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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)
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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.
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Funding Scheme
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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
NG7 2RD Nottingham
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.