Dr Martin McPhillie

Profile

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, performing multi-parameter lead optimisation to progress this series towards preclinical development.

I became a Teaching Fellow in Organic Chemistry at the School of Chemistry, Leeds in 2017. I have since combined this role with research supervision of PhD students and Postdocs, whilst supporting Professor Colin Fishwick in his role as Head of School. In 2022, I became a Lecturer in Organic Chemistry as part of the University’s Curriculum Redefined project.

Responsibilities

• BSc & MChem Medicinal Chemistry Programme Manager
• Curriculum Redefined Lecturer
• Module Leader for CHEM3146 & CHEM1200

Research interests

My research interests lie in the areas of 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. I am a UKRI co-investigator with active research projects which focus on designing antibacterial and antiviral compounds, to treat Gram-negative infections, SARS-CoV-2 and non-polio enterovirus. Our work is funded by the MRC, BBSRC, NIH and Diabetes UK. Medicinal chemistry is underpinned by a strong foundation in organic chemistry so much of our work involves synthetic chemistry and bespoke compound/library 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.

Qualifications

• PhD, University of Leeds (2012)
• MChem (Ind), University of Leeds (2008)

Professional memberships

• AMRSC

Student education

I am the programme manager for the BSc and MChem Medicinal Chemistry courses at Leeds and the module leader for CHEM3146 Medicinal Chemistry, CHEM1200 Extraordinary Chemistry and LISS1029 Natural Science as part of the International Summer School.

I teach on the following modules/courses: CHEM2215, Advanced Topics (CHEM560X), MSc Chemical Biology & Medicinal Chemistry. In addition, I am the co-manager of level 3 practical labs, with a focus on the non-lab content.

I am a BSc, MChem and MSc research project supervisor. If you are interested in medicinal chemistry and/or computer-aided drug design projects, please contact me.

Research groups and institutes

• Chemical Biology and Medicinal Chemistry

Current postgraduate researchers

• Qi You