| EPSRC Reference: |
GR/R69488/01 |
| Title: |
The Total Synthesis of Thapsigargin |
| Principal Investigator: |
Ley, Professor S |
| Other Investigators: |
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| Project Partners: |
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| Department: |
Chemistry |
| Organisation: |
University of Cambridge |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 March 2002 |
Ends: |
28 February 2005 |
Value (£): |
189,103
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| EPSRC Research Topic Classifications: |
| Asymmetric Chemistry |
Biological & Medicinal Chem. |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
No relevance to Underpinning Sectors |
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| Panel History: |
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Summary on Grant Application Form |
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The medicinal properties of the Mediterranean plant Thapsia garganica L. were first recognised in the second century BC. In 1976 sixteen guaianolides collectively termed `thapsigargins', were isolated. Thapsigargin is a potent histamine liberator and a selective and irreversible inhibitor of the sarcoplasmic and endoplasmic reticulum Ca2+ ATP dependant pumps (SERCAs) at nanomolar concentrations. It demonstrates a remarkable specificity for the SERCA isozymes, and any entity selectively effecting a specific step in Ca 2+ homeostatis is a potential tool for investigating and manipulating the physiology of the cell. The selectivity of thapsigargin in this inhibitory capacity has led to it becoming a powerful tool to manipulate intracellular Cat+.To date, no total synthesis has been published, although some minor modifications have been made possible through degradation studies. A flexible synthetic route to the thapsigargins would allow the synthesis of a range of guaianolides, their analogues and specifically labelled derivatives (useful for metabolic studies) in which the label is incorporated into the skeleton of the molecule. These materials would be invaluable tools in the study of Ca 2+ dependant cellular processes.
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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.cam.ac.uk |