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Details of Grant 

EPSRC Reference: EP/S028722/1
Title: Supramolecular Designs on Dynamic Covalent Protein Recognition
Principal Investigator: Thompson, Dr S
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Sch of Chemistry
Organisation: University of Southampton
Scheme: New Investigator Award
Starts: 01 April 2019 Ends: 31 March 2021 Value (£): 244,859
EPSRC Research Topic Classifications:
Biological & Medicinal Chem. Chemical Biology
Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:
Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Panel DatePanel NameOutcome
24 Jan 2019 EPSRC Physical Sciences - January 2019 Announced
Summary on Grant Application Form
This project describes a strategy for the development of a 'toolkit' of covalent chemical probes for the inhibition of therapeutically-relevant protein-protein interactions (PPIs) that are critical in myriad diseases. The project will develop molecules that have been carefully designed to adopt a particular shape such that they can mimic the recognition of one protein surface by another, bind to the protein, and then carry out a modification on the protein in question to add a new group of atoms to a particular site. The mimic molecules will be configurable to selectively recognise different protein surfaces as desired. The modification will be carried out by a reactive group on the mimic molecules containing a boron "acceptor" and they will be targeted to modify the side-chain of a specific amino acid on the protein in question - usually one containing an oxygen or nitrogen atom "donor". This 'toolkit' of chemical probes (the mimics) represents a fundamentally new way of targeting non-enzymatic proteins. The agents will be tuneable to bind via either a dynamic or irreversible covalent mechanism. Their utility as a general method for mediating therapeutically-relevant protein-protein interactions (PPIs) will be evaluated using a particular protein system (Hif1alpha/p300) that is important in the hypoxic response and in many solid-tumour cancers. Beyond their use as disruptors of PPIs the approach holds great promise for: (i) mediating protein misfolding, (ii) site-specific protein labelling, (iii) bio imaging, (iv) tumour targeting, (v) therapeutic depletion, and (vi) protein mapping.
Key Findings
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Potential use in non-academic contexts
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Impacts
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Summary
Date Materialised
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Project URL:  
Further Information:  
Organisation Website: http://www.soton.ac.uk