| EPSRC Reference: |
GR/R89257/01 |
| Title: |
Novel glucose cyclophosphate and multisubstrate adduct derivatives: Putative inhibitors of MIP synthase |
| Principal Investigator: |
Migaud, Professor ME |
| Other Investigators: |
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| Department: |
Sch of Chemistry and Chemical Eng |
| Organisation: |
Queen's University of Belfast |
| Scheme: |
Fast Stream |
| Starts: |
01 July 2002 |
Ends: |
30 June 2005 |
Value (£): |
59,922
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
Chemical Biology |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
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SummaryDescribe the proposed research in about 200 words.Myo-inositol 1-phosphate (MIP) synthase is the enzyme responsible for the de-novo production of MIP, precursor to the second messenger inositoi-1,4,5triphosphate (1133). This enzyme converts glucose 6-phosphate into MIP with the catalytic intervention of nicotinamide adenine dinucieotde (NAD). During the catalytic conversion, glucose 6-phosphate is oxidised to 5-keto-glucose 6-phosphate with concomitant reduction of NAD to NADH. It has recently bean proposed that the subsequent enolisation of 5-keto-glucose 6-phosphate was catalysed infra-molecularly by the phosphate moiety, rather than by a basic residue present in the catalytic pocket. To establish the nature of the transition state required for enolisation and design potent slowly reversible and irreversible inhibitors of MIP synthase, novel mechanism-based and multisubstrate adduct analogues of glucose and glucitol-6-phosphate will be synthesised and evaluated in-house as putative inhibitors of yeast MIP synthase. Further biological assays of these analogues will be carried out on tuberculosis bacterium MIP synthase. In vivo inhibition of the synthase could provide insights in its pharmacological importance to neuronal communication and a pharmcal alternative to the treatment of manic disorders by Li+. Alternatively, its inhibition could provide new opportunities to combat tuberculosis since MIP is one of the building blocks of the bacterium cell wall.
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Potential use in non-academic contexts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
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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.qub.ac.uk |