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PhD Studentship: Copper(II)-Catalyzed Atom and Step Economical Late Stage Functionalisation of Bioactive Compounds

University of Sussex - Chemistry

Qualification Type: PhD
Location: Falmer
Funding for: UK Students
Funding amount: Home tuition fees and stipend at standard UKRI rates
Hours: Full Time
Placed On: 26th January 2023
Closes: 20th February 2023
 

A PhD studentship (3.5 years) is available from September 2023 under the supervision of Dr George Kostakis, Chemistry department, School of Life Sciences.

Deadline: 20th February 2023

Project Title: Copper(II)-Catalyzed Atom and Step Economical Late Stage Functionalisation of Bioactive Compounds.

Brief Description of the Project:

Synthetic chemists have always been fascinated with creating molecular complexity from readily available starting materials. The typical cost of developing a drug is over 2 billion USD and the time required to reach the market is approximately 14 years. With a very high attrition rate, faster, more economical processes for creating these entities are welcome. Selective processes that lead to the correct shape of the drug ensure that it fits correctly in its 3D-biological chiral protein target. Moreover, drugs need to be made on a large scale. We have recently described a series of metal catalysed multicomponent reactions that are “atom economical”, using all atoms to create complicated architectures with 3D shapes, to complement the complexity of protein targets. Moreover, the catalytic nature ensures that energy use, waste production, solvent use are minimal, so have the potential for largescale production. Also, the catalysts are very easy to make and are stable in air, making them

readily available and scalable, and the fact that we can monitor and optimise new reactions without requiring expensive inert gases. We aim to demonstrate that these catalytic reactions have real-world applications as in the design of PROTAC (proteolysis targeting chimeras) molecules for targeted protein degradation, an area of intense current academic and commercial interest. PROTACs induce the ubiquitination machinery to tag a protein for recycling by the proteasome. Structurally guided drug design and biological assays can form a feedback loop to our synthetic chemistry where we can optimise the PROTACs to improve their selectivity and properties, such as solubility, permeability, and stability. These findings will profoundly influence the design and optimisation of PROTACs and linker chemistry in general, and the combination of academic groups with leading UK industrial partners will enable us to attain our goals.

How to apply:

Please submit a formal application using the online admissions portal attaching a CV, degree transcripts and certificates, personal statement, and two academic references. A research proposal is not required.

On the application system select Programme of Study – PhD Chemistry. Please state the project title under funding obtained and the supervisor’s name where required.

Candidates must have or expect to obtain a minimum 2:1 undergraduate degree. An MSc degree will be advantageous. Your qualification should be in chemistry or a related subject area. You may also be considered for the position if you have other professional qualifications or experience of equivalent standing.

Candidates for whom English is not their first language will require an IELTS (or equivalent) score of 6.5 overall, with not less than 6.0 in any section.

Please check our Admissions page for further information: Chemistry PhD : University of Sussex

For enquiries about the application process, contact Emma Chorley: lifesci-rec@sussex.ac.uk

For enquiries about the project, contact Supervisor: g.kostakis@sussex.ac.uk

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