| EPSRC Reference: |
GR/R82302/01 |
| Title: |
Conotoxins Mimics - Synthesis of Peptoids with Potent Neurological and Neuromuscular Activity. |
| Principal Investigator: |
McKendrick, Dr J |
| Other Investigators: |
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| Department: |
Chemistry |
| Organisation: |
University of Reading |
| Scheme: |
Fast Stream |
| Starts: |
01 October 2002 |
Ends: |
30 September 2005 |
Value (£): |
62,171
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
Biomedical neuroscience |
| Chemical Biology |
Chemical Synthetic Methodology |
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| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
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the search for new pharmaceutically active molecules has led to the discovery of a wide range of marine organisms that produce a myriad of active components. The venom of he cone snail has become an important source of a large number of structurally unique, biologically active peptides, most )f which target the neuromuscular or neuronal acetylcholine receptors. The programme described plans to explore the nature of the inhibition of the neuromuscular nicotinic acetylcholine receptor (nAhR) alpha-1 beta-1 gamma delta by conotoxin alphaGl, the smallest yet described ion channel blocking peptide. The research will aim to mimic the unique structure of the peptide through replacement of the constraining disulfide bridges with carbon double bonds with a view to producing a more stable and more potent inhibitor. Exploration of the use of carbon-carbon double bonds is mimics of the S-S bridges present in alphaGl will be undertaken to determine the optimum replacement for retention of the overall structural motif. It s our intention to produce the carbon-carbon double bond constraints using olefin metathesis as a way of enabling the correct folding of the linear precursor under thermodynamic conditions. Subsequent parallel synthesis studies, will allow the optimization of the structure for receptor fit and for Optimum residue contacts, thereby enhancing the potency of the inhibitor.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.rdg.ac.uk |