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Smart Bioisosteres: Beyond a spatial mimic to improved plant biology

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

Project Description

Bioisosteres are essential alternative design options in the development of new agrochemicals, to retain or improve overall biological properties of an active ingredient, such as activity, biokinetics, nd metabolic stability. However, the development of bioisosteric replacements for linking groups (not directly involved in binding to the protein target) has to date focused exclusively on their scaffolding properties, to mimic topology, and neglected the effect on the properties of the substituents directly attached to the scaffold (e.g. pKa or H-bonding potential, hybridisation). In developing new agrochemicals, these substituent features are crucial to the progress of a compound, and notably the potential to reach the relevant site of activity. This project will design, synthesise and assess new bioisosteres. It will examine the change in the physicochemical and ADME properties the bioisosteres can confer to a compound as a whole (logP, solubility, metabolic stability), as well as the particular changes to the key functional substituents on the scaffold, providing new insights to these materials.

Advantageous scaffolds will be incorporated into known agrochemical compounds for further investigation including in vitro enzyme assays, whole plant studies and X-ray studies.

The project would suit a candidate with experience in synthetic chemistry and interests in the application to plant chemical biology.

Supervisory Team

Dr James Bull (https://www.imperial.ac.uk/people/j.bull )
Dr James Murray (https://www.imperial.ac.uk/people/j.w.murray)
Bill Whittingham (https://www.linkedin.com/in/will-whittingham-a8495523/?originalSubdomain=uk)

Funding Notes

This studentship is co-funded by Syngenta.

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