Synthetic Organic Approaches for Covalent Inhibition of Protein-Protein
We are looking for an enthusiastic and well-organized student with an interest in applying the full range of synthetic organic chemistry methods to design and construct conformationally well-defined molecules (foldamers) that covalently recognise key elements of protein surfaces. These scaffolds will form a toolkit of chemical probes for proteins that lie at the heart of intractable disease. Specific objectives of the project are: (i) the design, synthesis, and characterisation of new peptidomimetic scaffolds bearing covalent warheads; (ii) investigation of their ability to mediate the behaviour of therapeutically-relevant proteins; (iii) ‘catch and modify’ – chemical post-translational modification of amino acid side-chains.
Prior experience in Chemical Biology or Medicinal Chemistry is not required, but training in these areas will be provided for interested students during the PhD.
Background – structure and function in Nature
The inspiration and motivation for research in the group derives from the exquisite control that Nature exerts over structure and function – at both atomic and macromolecular levels. Unmet challenges in biology and medicine stem from gaps in our understanding of the basic science underlying these processes and a shortage of chemical tools for the interrogation and manipulation of specific interactions. Proteins constitute a bio-macromolecular class of particular interest due to their essential roles in all life forms, performing myriad structural, catalytic, and signalling functions. They are critically important in numerous disease states including cancer, diabetes, and neurodegeneration.
Organic synthesis as a key tool
Our major long-term goals are to develop a deeper understanding of the structure/function relationships governing therapeutically relevant protein-protein interactions (PPIs) and protein-misfolding conditions, and to develop molecular tools for their manipulation. In our group organic synthesis and methodology are central tools allied with rigorous structural and conformational assignment by solution- and solid-phase methods (especially NMR and X-ray). Combined with techniques from the fields of supramolecular chemistry, physical organic, and chemical biology this makes for multi-disciplinary projects. We have established collaborations with experts in molecular- and cellular-biology, providing insights into the behaviour of our chemical probes in physiologically relevant settings.
The project is funded for 3 years and welcomes applicants from the UK and EU who have or expect to obtain a first or upper second class degree (or equivalent) in chemistry. Funding will cover full fees and a tax-free stipend at current research council rates of £ 14,777 per annum.
Due to funding restrictions this position is only open to UK/EU applicants who meet the RCUK eligibility criteria
Applications for a PhD in Chemistry should be submitted online at https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Search
Ensure you select the academic session 2018/19 on the Research radio button. Enter Chemistry in the search text field.
Insert Sam Thompson in the field for proposed supervisor.
If you are interested in the position and would like to find out more contact Dr Sam Thompson directly ([Email Address Removed]). Any queries on the application process should be made to [Email Address Removed]
Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified.
For recent relevant publications see:
Curr. Opin. Chem. Biol. 2018, 44, 30-38.
Chem Sci. 2016, 7, 6435-6439.
Angew. Chem. Int. Ed. 2015, 54, pp. 2649-2652.
Angew. Chem. Int. Ed. 2014, 53, pp. 3650-3653.