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Bioscience for Renewable Resources for Medchem and Toward Sustainable Pharmaceutical Molecule Manufacture

  • Full or part time
  • Application Deadline
    Monday, April 13, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

There is a need for novel and renewable technologies to enable the sustainable manufacture of pharmaceuticals. Enzymes offer a matchless opportunity for selective synthesis and late stage functionalisation, they also offer a sustainable, green and cost-effective approach toward synthesis. This project brings together two collaborative partners to harness the power of enzymes for drug discovery through fragment based screening and late stage functionalisation approaches.
Concept Life Science use the powerful approach of fragment-based design to enable discovery of pharmaceutical leads. Such fragments require linking together to form the bioactive molecule for testing.
The Goss group are expert in biotransformations and identifying novel halogenases, and have identified the first halogenase with a preference for iodination. This enzyme accepts a broad range of substrates.[1] They have also demonstrated the first application of enzymatic halogenation and cross-coupling – enabling the development of halogenation/cross-coupling cascades.[2]

With a focus on antibiotics and anticancer agents, in this project we will explore the application of renewable and disruptive enzymatic halogenation technologies to medicinal chemistry and molecule manufacture. By applying combinations of enzymatic and cross-coupling steps we will enable not only late stage functionalisation of identified pharmaceutical candidates, including natural products, but also enable the assembly of series of identified fragments through halogenation/cross-coupling cascades.
The project will consist of:
1) fragment-based library analysis and screening
2) informatics led halogenase discovery, and halogenase assay with series of fragments and leads
3) cross-coupling of fragments and cross-coupling to enable late stage diversification

Funding Notes

Dr Tom Pesnot from Concept Life Science will be second supervisor.

Concept Life Sciences is a drug discovery and development service provider principally for the pharmaceutical sector.


[1] A Marine Viral Halogenase, that Iodinates Diverse Substrates
Danai S. Gkotsi, Hannes Ludewig, Sunil V. Sharma, Jack A. Connolly, Jagwinder Dhaliwal, Yunpeng Wang, William P. Unsworth, Richard J. K. Taylor, Matthew M. W. McLachlan, Stephen Shanahan, James H. Naismith & Rebecca J. M. Goss*
Nature Chemistry, 2019, 11, 1091- 1097

Highlighted in C.&EN.:

[2] Gene expression enabling synthetic diversification of unnatural products:chemogenetic generation pacidamycin analogs
Deb Roy, S. Grüschow, N. Cairns, R. J. M. Goss*, J. Am. Chem. Soc., 2010, 134, 1224-12245.
Highlighted in C.&EN. News, August 23rd, 2010.

How good is research at University of St Andrews in Chemistry?
(joint submission with University of Edinburgh)

FTE Category A staff submitted: 37.30

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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