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Identification and optimisation of small molecule inhibitors of a novel thrombin-like protease for the treatment of thrombosis

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  • Full or part time
    Dr Foster
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

This project seeks to identify and develop small molecule inhibitors of a hitherto unexplored serine protease as potential therapeutics for the treatment of thrombosis. Recent prominent studies suggest the enzyme’s importance in the treatment of thrombosis with minimal bleeding risk. Thrombosis is not treated effectively with existing therapeutics and as such there is a great need to validate new agents for potential therapeutic intervention. Here, we intend to identify and develop small molecule inhibitors of the target using fragment-based approaches led by computational design and synthetic chemistry and to investigate the mechanism of small molecule inhibition through use of biophysical investigation and activity-based chemoproteomics. The student will be engaged in a vibrant, multidisciplinary environment and will develop skills in medicinal chemistry, computer-aided drug design and cardiovascular biology.
Plan of Investigation:
• Identify and optimise novel small molecule inhibitors with appropriate in-vitro and in-vivo efficacy through use of fragment-based design
• Identify both competitive and allosteric inhibitors of the target
• Investigate novel structure-guided methods for fragment-based design
• Investigate the mechanism of small molecule inhibition through use of affinity- and activity-based chemoproteomics

The project would suit a student with general interests at the interface between chemistry and biology and more specifically medicinal chemistry and chemical biology.

Funding Notes

The position is competition funded through a MRC-funded DTA. For further details see. http://medhealth.leeds.ac.uk/info/1450/scholarships/1511/mrc_dtp_studentships

References

http://www.chem.leeds.ac.uk/People/Foster.html

Related Subjects

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FTE Category A staff submitted: 34.40

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