Dr Martin McPhillie
I am a medicinal chemist working in the area of anti-infective drug discovery. My expertise lies in structure-based molecular design performing (i) de novo ligand design to generate putative inhibitors of target enzyme(s) (ii) in silico molecular docking to evaluate possible inhibitor conformations (iii) virtual high-throughput screening to identify putative ligands from commercial sources or in-house libraries. This stems from an understanding of protein structure and function, and utilising bioinformatics. In parallel, I have a broad knowledge of modern organic synthesis and medicinal chemistry.
My first experience of research was an industrial placement at Avecia Pharmaceuticals, Huddersfield (formerly Zeneca) under the supervision of Prof John Blacker, Drs Neil Edwards and Nick Powles. I assisted in optimising the manufacturing route of the hypertension drug Diltiazem using catalytic asymmetric transfer hydrogenation. I then return to Leeds for my MChem year and a methodology research project with Prof Steve Marsden, and subsequently studied for a PhD at the Astbury Centre, Leeds (supervisors Profs Colin Fishwick & Ian Chopra) in the hit identification and optimisation of novel small molecules inhibitors of bacterial RNA polymerase using structure-based molecular design, medicinal chemistry and microbiology. During my final year I was fortunate to undertake a short secondment to Prof Marv Miller's laboratory at the University of Notre Dame, USA to synthesize antibacterial siderophore-small molecule conjugates.
My first Postdoctoral Research position took me to the University of Sheffield under the supervision of Prof David Rice & Dr Stephen Muench, optimising inhibitors of enoyl-reductase in apicomplexan parasites. Here I developed a collaborative approach to research working closely with PIs from the University of Chicago, University of Strathclyde, Johns Hopkins University and WRAIR, coordinating all project data. My second postdoc took me back to Leeds working with Profs Peter Johnson, Philip Kocienski and Colin Fishwick on the lead optimisation of novel Plasmodium DHODH inhibitors. During this work, I played a central role in the development of the current late-lead series of DHODH inhibitors, which are now progressing toward preclinical development.
I became a Teaching Fellow in Organic Chemistry at the School of Chemistry, Leeds in 2017.
- Organic Tutor & Lab Staff Demonstrator
- Advanced Topic Lecturer
- Research Fellow in Medicinal Chemistry
My interests lie in medicinal chemistry and computer-aided drug design. As such our research is multidisciplinary, working closely with structural biologists and microbiologists. A common theme is the identification of new small molecule inhibitors as anti-infective agents. We are currently working on projects focussing on designing antibacterial, antiviral and anti-parasitic compounds, to treat Gram-negative infections, Ebola and malaria respectively. Medicinal chemistry is underpinned by a strong foundation in organic chemistry so much of our work involves synthetic chemistry and bespoke compound synthesis. This is integrated with computer-aided drug design, where our compound synthesis is guided by molecular modelling using crystal structures of the proteins of interest.