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Details of Grant 

EPSRC Reference: GR/M74696/01
Title: NOVEL APPROACHES TO LACTACYSTIN & ITS ANALOGUES
Principal Investigator: Hayes, Professor CJ
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Sch of Chemistry
Organisation: University of Nottingham
Scheme: Standard Research (Pre-FEC)
Starts: 06 October 1999 Ends: 05 October 2002 Value (£): 52,702
EPSRC Research Topic Classifications:
Biological & Medicinal Chem. Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:
Pharmaceuticals and Biotechnology No relevance to Underpinning Sectors
Related Grants:
Panel History:  
Summary on Grant Application Form
The natural product lactacystin was discovered because of its ability to induce neurite outgrowth in the murine neuroblastoma cell line Neuro-2a and it was later shown that lactacystin was an inhibitor of the 20S proteasome. The proteasome is a multi-subunit protein present in most cell types and is responsible for the degradation of most cellular proteins. It is involved in a large number of cellular processes including cell cycle control, cell differentiation and the immune response. Because of this biological activity there is much interest in developing therapeutics based upon the structure of lactacystin. Our research will involve developing novel synthetic methodology for the rapid synthesis of lactacystin and a range of designed structural analogues which may be of therapeutic value. We plan to use a regio- and stereoselective alkylidene carbene-mediated 1, 5 C-H insertion reaction as the key stratagem for the asymmetric synthesis of the a, a -dialkyl-a-amino acid moiety present in lactacystin.
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Organisation Website: http://www.nottingham.ac.uk