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Details of Grant 

EPSRC Reference: EP/N034260/2
Title: Substrate Peptidomimetic Inhibitors (SPIs) of the COP9 signalosome
Principal Investigator: Jamieson, Dr A
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Domainex Ltd
Department: School of Chemistry
Organisation: University of Glasgow
Scheme: Standard Research
Starts: 01 June 2018 Ends: 30 November 2019 Value (£): 189,897
EPSRC Research Topic Classifications:
Biological & Medicinal Chem.
EPSRC Industrial Sector Classifications:
Pharmaceuticals and Biotechnology Healthcare
Related Grants:
EP/N034295/1
Panel History:  
Summary on Grant Application Form
The aim of the proposed research is to develop a novel type of molecule that will allow validation of a family of enzymes called deubiquitylases (DUB) as therapeutic targets in oncology and provide lead compounds to initiate an anticancer drug discovery programme.

DUBs play a major role in the cell by removing the small regulatory protein called ubiquitin from other proteins. The human genome codes for around 80 deubiquitylases (DUB/DUB-like). This enzyme family contains five sub-families, four of which have been studied and targeted previously. The remaining group are called Zn-dependent DUBs and have not been targeted due to a lack of molecules that can be used to probe their function.

We have established a team of experts in their respect research fields (Echalier - Structural Biology, Jamieson - peptide chemistry & Kessler - protein mass spectrometry) to develop such molecules based on the natural peptide substrates of the enzymes. Using modern synthetic chemistry techniques we aim to produce a range of molecules that target Zn-dependent DUBs with unprecedented selectivity. The insights gained from these experiments will be used to validate them as a therapeutic target, and inform structure-based drug design of selective DUB inhibitors.

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Organisation Website: http://www.gla.ac.uk