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EPSRC Reference: GR/S46970/01
Title: Exploiting the Effects of Catalytic Microenvironments in Synthetic Enzyme Mimics
Principal Investigator: Hollfelder, Dr F
Other Investigators:
Researcher Co-Investigators:
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Department: Biochemistry
Organisation: University of Cambridge
Scheme: First Grant Scheme Pre-FEC
Starts: 05 January 2004 Ends: 04 December 2006 Value (£): 124,133
EPSRC Research Topic Classifications:
Catalysis & Applied Catalysis Physical Organic Chemistry
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
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Summary on Grant Application Form
The remarkable catalytic proficiency of enzymes is ascribed to a combination of effects, including contribution from the active site medium. We aim to describe, quantify and exploit medium effects for catalysis in artificial enzyme mimics. In past work we have used polyethylene imines (PEIs) with modified surfaces (creating active microenvironments) to bring about efficient catalysis with rate accelerations per site up to 106 for a proton transfer reaction. We now want to extend this to phosphate transfer catalysis. We will use a combination of high-throughput synthesis and high-throughput assays to identify successful catalysts from diverse libraries. containing PEIs with pendant hydrophobic, positive and negative groups, possibly coordinated to metal ion cofactors. In preliminary studies we have observed structure-activity relationships and modest catalysis in the presence of a metal ion for phosphate monoester hydrolysis. We will study this and in particular intramolecular reactions and analyse the catalytic solutions identified in kinetic detail.
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Organisation Website: http://www.cam.ac.uk