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Using chemical models to characterize potential specific medium effects in active sites of enzymes

Objective

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 the Hollfelder group used polyethylene imines (PEIs) with modified surfaces to bring about efficient catalysis with rate accelerations per site up to 10e6 for a proton transfer reaction, thus creating active microenvironments.

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. Of particular interest will be the catalysis of phosphate transfer, for which we want to quantify the potential of medium effects. Our ultimate focus will be on kinetic analysis the catalytic solutions identified in structure-activity relationships for our combinatorial libraries.

Call for proposal

FP6-2002-MOBILITY-5
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Funding Scheme

EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Address
The Old Schools, Trinity Lane
Cambridge
United Kingdom