Dr Christopher R Coxon

Dr Christopher R Coxon (MChem, PhD)

Senior Lecturer in Medicinal Chemistry

Tel: 0131 651 7112
Email: chris.coxon@ed.ac.uk

School of Chemistry

Street: Room 278
University of Edinburgh
Joseph Black Building
David Brewster Road
Edinburgh
EH9 3FJ
City
Post code

Biography

Background

Dr Chris Coxon completed his PhD as part of the Cancer Research UK Medicinal Chemistry Training Programme at the Northern Institute for Cancer Research, Newcastle University (2010), where he was involved with designing selective small molecule inhibitors of protein kinases e.g. cyclin-dependent kinases and Nek2 that are involved in cancer. He also began his interest here in the use of fluorine in organic chemistry. Chris then moved to Durham University in 2010 to work as a postdoctoral research associate in the areas of synthetic organic chemistry and chemical biology under Prof. Patrick Steel, where he identified and developed new small molecule chemical agents to sensitise multiple herbicide resistant weeds e.g. 'black grass' to crop control measures - a major challenge in wheat production. In Oct 2012 he joined Prof. Steven Cobb’s group (Durham University) as a PDRA, where he became interested in peptide chemistry and developing new peptide modification, fluorination and cyclisation methods. In 2013 Chris began his independent research career as a Temporary Lecturer at Durham University, also running the School of Chemistry chromatography facility, before being appointed to a permanent position of Lecturer in Medicinal and Natural Products Chemistry at Liverpool John Moores University in October 2014, where he was awarded the Vice Chancellor’s Medal for Research and Scholarship (2019). In 2019, Chris moved to Scotland to take up the position of Associate Professor in Synthetic Chemistry at Heriot-Watt University (Edinburgh) as a Bicentennial Research Leader. He finally, moved to University of Edinburgh, School of Chemistry in August 2021 as Senior Lecturer in Medicinal Chemistry and Director of the MSc in Medicinal and Biological Chemistry. Chris is also the Co-founder and Director of Pepmotec Ltd – a peptide modification spin-out company based in Durham.

Qualifications

MChem

PhD

Responsibilities & affiliations

Programme Director of MSc in Medicinal and Biological Chemistry

Research

Research summary

The Coxon Lab is interested in developing new medicines, detecting and diagnosing disease and understanding how diseases work at the molecular level by designing and testing chemical probes. We have a specific interest in neurological and neurodegenerative diseases, such as migraine, chronic pain and Parkinson’s disease; but also work on drug targets relating to infectious disease virulence and diabetes.

Our lab has specific expertise in drug design, peptide synthesis, drug metabolism and pharmacokinetics analysis, fluorine chemistry, NMR analysis of biological samples and tissues.

Research Overview

Medicinal Chemistry

1. Design and development of peptides to modulate secretin-like GPCRs involved in neurological and neurodegenerative disease

The secretin-like G protein-coupled receptor (GPCR) family bind endogenous signalling peptides in a number of physiological roles. However, several have been implicated in disease, therefore, we design peptides that can mimic the endogenous peptide to act as agonists (switching on the receptor) or antagonists (switching off the receptor).

One main interest is in the treatment of migraine - a chronic neurovascular disease that presents as a crippling headache and related sensory symptoms. In serious cases it can be debilitating and is considered by the WHO to be the 3rd most disabling disease in the world. It also costs the UK economy around £3.5 billion/year in lost workdays! Our lab has identified a series of synthetic peptides that can block the action of several G protein-coupled receptors (GPCRs) that play a role in migraine.

Current projects involve the optimisation of a) structure-activity relationships (SARs) using computational drug design, b) peptide synthesis, c) pharmacokinetic properties, d) target affinity and antagonist potency evaluation or e) synthesis of antagonists from nature.

Recent related papers:

Killoran, P.M., et al, Novel peptide calcitonin gene-related peptide antagonists for migraine therapy. J Pharm Pharmacol, 2023.
D'Aloisio, V., et al, The development and optimisation of an HPLC‐based in vitro serum stability assay for a calcitonin gene‐related peptide receptor antagonist peptide. J Peptide Sci, 2023, e3539.

2. Peptide-based inhibitors of bacterial transcription factors

A recent project in collaboration with colleagues in Infection Medicine at Edinburgh, seeks to optimise the efficacy of small peptides that inhibit a key bacterial transcription factor that is essential for virulence in listeria.

Current projects involve the optimisation of a) structure-activity relationships (SARs) using computational drug design, b) peptide pharmacokinetic properties, c) solid phase peptide synthesis and peptide modification.

Chemical biology

1. Fluorinated tools for chemical biology and biomarker detection

The incorporation of fluorine atoms into a biomacromolecule provides a background-free and environmentally sensitive reporter of structure, conformation, metabolism and interactions using 19F NMR (Figure 2). There are several methods to introduce the 19F reporter – either by synthetic incorporation via solid phase peptide synthesis, by genetic code expansion, or by post-translational bioconjugation or ‘fluorine-tagging’. We use fluorine-labelling to identify new starting points for medicinal chemistry and drug development. Our lab has also developed ways to label proteins and small molecules with fluorine so that we can detect and study protein misfolding/aggregation – part of the pathology of diseases like Alzheimer’s and Parkinson’s disease. Furthermore, we are interested in developing fluorinated chemical tools that can be used clinically for assessment of disease diagnosis, progression and severity in collaboration with clinicians in Emergency Medicine at the Edinburgh Royal Infirmary.

Projects involve developing new fluorinated chemical probes for 19F NMR, with which to investigate: a) the aggregation of disease relevant proteins, b) the activity or levels of enzymes in blood as biomarkers of disease, or c) for the identification of new ‘hit’ compounds that bind to and inhibit biological targets involved in disease, and use a combination of solid phase peptide synthesis, small molecule heterocyclic synthesis, protein expression and modification, 19F NMR biological assays, HPLC / mass spec analysis.

Recent related papers:

Hanson, G.S. et al., Fluorinated tags to study protein conformation and interactions using 19F NMR. ChemBioChem, 2024, 25, e202400195.
Killoran, P.M., et al., Probing peptidylprolyl bond cis/trans status using distal 19F NMR reporters. Chem Eur J, 2023, 29, p.e202203017.
Dognini, P., et al., 5, 10, 15, 20‐Tetrakis (pentafluorophenyl) porphyrin as a Functional Platform for Peptide Stapling and Multicyclisation. Chem Eur J, 2023, e202301410.
Verhoork, S.J., et al., Fluorinated prolines as conformational tools and reporters for peptide and protein chemistry. Biochemistry, 2018, 57, 6132-6143.