Synthesis and Drug Development of Small Molecule Inhibitors of PTP1B for the Treatment of Obesity-related Co morbidities

Faculty of Health & Wellbeing, Sheffield Hallam University
Biomolecular Sciences Research Centre
PhD Research Studentship (full-time for 3 years)
Stipend: £14,777 per annum

A three-year PhD studentship is available to UK and EU students. The studentship covers home/EU tuition fees, stipend equivalent to full UK Research Council rate and research expenses.

Obesity causes insensitivity to the dietary hormone leptin and re activation of leptin receptors offers a therapeutic intervention for the co morbidities of obesity such as diabetes and hepatic steatosis.

The enzyme PTP1B is a negative regulator of both leptin and insulin receptors and inhibition of PTP1B thereby has potential for the development of new small molecule drugs.1,2

The successful candidate will work to discover, design and synthesise novel small molecule inhibitors of PTP1B with specific physicochemical properties.

The successful candidate will be trained in and gain high-level experience of:

• In silico screening, rational drug design and development of structure activity relationships based on crystal structures of PTP1B.
• Synthesis of compound libraries using established and novel synthetic/catalytic methodologies.
• Synthetic/catalytic reaction development and optimisation.
• Spectroscopic compound characterisation using a range of methods, including 1D and 2D multinuclear NMR and mass spectrometry.
• In vitro biochemical and cell based bioactivity and physicochemical assays.
• Interpretation and handling of assay data and use in informing further synthetic targets.

Candidate Profile:
The successful candidate should have (or expect) an honours degree at upper second class (2:1) or above in chemistry, biochemistry or a closely related discipline.

A solid background in organic and/or medicinal chemistry is essential and prior experience of chemical research would be advantageous.

Supervisory Team:
Principal Investigator / Director of Studies: Dr Danny Allwood
Research in the Allwood group focuses on the development of efficient synthetic and catalytic methods for the construction of highly 3 dimensional building blocks for application in drug discovery.

Co supervisor 1: Dr Nicola Aberdein
Dr Aberdein’s research is based in the molecular and cell biology of diet induced obesity, focusing on leptin signalling and PTP1B.

Co supervisor 2: Dr Alessandra Princivalle
Dr Princivalle’s research focuses on the molecular biology and pharmacology of conditions affecting the central nervous system.