| 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: |
12 August 2019 |
Ends: |
12 May 2022 |
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 Date | Panel Name | Outcome |
|
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 |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
|
Potential use in non-academic contexts |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
|
Impacts |
|
| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
|
| Date Materialised |
|
|
|
|
Sectors submitted by the Researcher |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
| Project URL: |
|
| Further Information: |
|
| Organisation Website: |
http://www.soton.ac.uk |