Christopher Coxon

Personal profile

Biography

Dr Coxon is Associate Professor in Synthetic Chemistry at Heriot-Watt University (since Sept 2019), appointed as part of the HW Bicentennial Research Leaders scheme. He is co-founder and Director of a Durham University peptide synthesis spin-out, Pepmotec Ltd and was awarded a prestigious Vice Chancellors Medal for Research and Scholarship (LJMU, 2019) for his research into new migraine treatments. He is a current panel member of the Royal Society of Chemistry Protein & Peptide Science Group and helps to organise the annual Early Stage Researchers’ meeting.

Dr Coxon has previously held academic appointments at Liverpool John Moores University (Senior Lecturer; Oct 14 - Aug 19) and Durham University (Aug 2013 - Sept 2014). Prior to undertaking postdoctoral positions at Durham, he completed his PhD (2010) at the Northern Institute of Cancer Research, Newcastle University as part of the Cancer Research UK Medicinal Chemistry Training Programme.

Research interests

The Coxon Lab (William Perkin 2.08)

Our Lab uses synthetic organic chemistry, peptide chemistry and fluorine chemistry to solve complex biological problems. Our researchers work in the following areas of medicinal and biological chemistry:

1. Understanding and treating intermittent and progressive neurodegenerative and neurological diseases.

(A) The role of the calcitonin gene related peptide (CGRP) in migraine pathophysiology and the development of novel therapeutics for migraine.

Our research programme has taken the native hormone, CGRP, that plays a key role in migraine and developed synthetic derivatives that are competitive antagomnists of CGRP. We use a range of in cell and in vivo assays to demonstrate the biological activity of these agents and are working to make these deliverable via nasal administration to treat migraine.

Relevant publications:

A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine. J. Pharm. Pharmacol. 2020, Bengt von Mentzer, Andrew F. Russo, Zhang Zhongming, Adisa Kuburas, Patrick M. Killoran, Vera D’Aloisio, Laura Nizic, Vicky Capel, David A. Kendall, Christopher R. Coxon, Gillian A. Hutcheon

Funding: Innovate UK/MRC Biomedical Catalyst Scheme

(B) Neurodegenerative diseases

We develop new responsive brain-targeting peptide assemblies that can a) deliver medicines to the brain, b) inhibit enzymes that are overactive in neurodegenerative diseases.

Relevant publications:

Development of Brain Targeting Peptide Based MMP-9 Inhibiting Nanoparticles for the Treatment of Brain Diseases with Elevated MMP-9 Activity. J. Pharm.Sci. 2020, IN PRESS, Yamir Islam, Khalid Aneesa, Stefano Pluchino, Muttuswamy Sivakumaran, Meritxell Teixidò, Andrew Leach, Amos A. Fatokun, James Downing, Christopher Coxon, Touraj Ehtezazi

Peptide based drug delivery systems to the brain. Nano Express, 2020, Islam, Y., Leach, A.G., Smith, J., Pluchino, S., Coxon, C.R., Sivakumaran, M., Downing, J., Fatokun, A.A., Teixidò, M. and Ehtezazi, T., 2020. 1

2. The fundamental basis of protein and peptide folding and it’s key role in healthy and disease processes.

Control of protein shape or conformation is essential for correct molecular recognition and precise function. Stabilisation of molecular structures can deliver potent interactions and new medicines. We are typically interested in gaining understanding from a chemical basis and treating neurological and neurodegenerative diseases. The group use a combination of a) model peptide synthesis, b) organofluorine chemistry, and c) F NMR techniques to study this. The molecular and biological basis of protein folding/mis-folding, which are a characteristic feature of a class of diseases called proteopathies, which includes several neurodegenerative diseases e.g. Alzheimer’s, Parkinson’s etc.

Relevant publications:

Fluorinated prolines as conformational tools and reporters for peptide and protein chemistry. ACS Biochem. 2018, 57(43), 6132-6143, Sanne J.M. Verhoork, Patrick M. Killoran and Christopher R. Coxon

3. Using perfluorinated scaffolds to stabilise bioactive 3D peptide architectures

We have explored the use of the highly-reactive reagent, hexafluorobenzene, as a template for peptide modification/arylation/cyclisation towards new biologically active molecules for medicine and for miniaturised diagnostic reagents that can compete with existing antibody methodologies.

Relevant publications:

Using ¹⁹F NMR and two-level factorial design to explore thiol-fluoride substitution in hexafluorobenzene and its application in peptide stapling and cyclisation. Pept. Sci. 2020 IN PRESS. Paolo Dognini, Patrick M. Killoran, George S. Hanson, Lewis Halsall, Talhat Chaudhry, Zasharatul Islam, Francesca Giuntini and Christopher R. Coxon

Tuning the Binding Affinity and Selectivity of Perfluoroaryl‐Stapled Peptides by Cysteine‐Editing. Chem. Eur. J. (HOT PAPER), 2019, 25(1):177-182. Sanne J. M. Verhoork Dr. Claire E. Jennings Neshat Rozatian Dr. Judith Reeks Jieman Meng Emily K. Corlett Fazila Bunglawala Prof. Martin E. M. Noble Dr. Andrew G. Leach Dr. Christopher R. Coxon
2,2,2-Trifluoroethanol as a solvent to control nucleophilic peptide arylation. Org. Biomol. Chem. 2017, 15, 4081-4085. Diana Gimenez, Anica Dose, Nicholas L. Robson, Graham Sandford, Steven L. Cobb and Christopher R. Coxon
The application of perfluoroheteroaromatic reagents in the preparation of modified peptide systems. Org. Biomol. Chem. 2017, 15, 4086-4095. Diana Gimenez, Caitlin A. Mooney, Anica Dose, Graham Sandford, Christopher R. Coxon and Steven L. Cobb

Funding: EPSRC - Royal Society

4. The development of novel synthetic methodologies towards non-natural amino acids

We develop new methodologies towards, for example, fluorinated amino acids or novel tryptophan derivatives for new antibiotics.

Relevant publications:

Synthesis, Ni(II) Schiff base complexation and structural analysis of fluorinated analogs of the ligand (S)-2-[N-(N′-benzylprolyl)amino]benzophenone (BPB). J. Fluor. Chem. 2015, 173, 77-83. Natalie J. Tatum, Dmitry S. Yufit, Steven L. Cobb and Christopher R. Coxon

External positions

Director and co-founder of Pepmotec Ltd

1 Feb 2019 → …

RSC Protein & Peptide Science Group Committee

2019 → …

SCI Young Chemists Panel

2016 → 2018

Keywords

QD Chemistry

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Research Output

20 Article
2 Patent
1 Review article

2-Arylamino-6-ethynylpurines are cysteine-targeting irreversible inhibitors of Nek2 kinase

Matheson, C. J., Coxon, C. R., Bayliss, R., Boxall, K., Carbain, B., Fry, A. M., Hardcastle, I. R., Harnor, S. J., Mas-Droux, C., Newell, D. R., Richards, M. W., Sivaprakasam, M., Turner, D., Griffin, R. J., Golding, B. T. & Cano, C., Jun 2020, In : RSC Medicinal Chemistry. 11, 6, p. 707-731 25 p.