Dr Christopher R Coxon

Senior Lecturer in Medicinal Chemistry

Contact details



Room 278
University of Edinburgh
Joseph Black Building
David Brewster Road

Post code

Research summary

Medicinal chemistry; peptide chemistry, fluorine, neurological and neurodegenerative disease

Research Overview

Our Lab uses synthetic organic chemistrypeptide chemistry and fluorine chemistry to solve complex medical and 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.

The calcitonin gene related peptide (CGRP) plays a key role in migraine. Our research programme has taken the native hormone and developed short synthetic derivatives that are competitive antagonists of CGRP. We use a range of cellular and in vivo assays to optimise the biological activity and ‘drug-like’ properties (e.g., metabolic liability, plasma protein binding and water solubility) of these agents and are working to make these deliverable via nasal administration as a rapid, abortive therapy for migraine.

Relevant publications:

Funding: Innovate UK/MRC Biomedical Catalyst Scheme, Carnegie Trust, Royal Society of Chemistry

Check out our recent Application Note working with Teledyne Isco to develop flash purification of peptide-peptoid hybrids.

(B) Neurodegenerative diseases

Possibly the greatest medical need is for new ways to treat or slow the progression of a wide range of neurodegenerative diseases, e.g., Alzheimer’s and Parkinson’s disease. For a drug to access the brain, which is protected by the blood brain barrier is a significant obstacle in treating these diseases. We explore and develop new responsive brain-targeting peptide assemblies that can a) deliver novel medicines to the brain, and b) inhibit enzymes that are overactive in neurodegenerative diseases.

Relevant publications:

2. The fundamental basis of protein and peptide folding and its 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:

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

Funding: EPSRC, Royal Society

  1. D’Aloisio, V., Dognini, P., Hutcheon, G.A. and Coxon, C.R., 2021. PepTherDia: database and structural composition analysis of approved peptide therapeutics and diagnostics. Drug Discovery Today.
  2. von Mentzer, B., Russo, A.F., Zhang, Z., Kuburas, A., Killoran, P.M., D’Aloisio, V., Nizic, L., Capel, V., Kendall, D.A., Coxon, C.R. and Hutcheon, G.A., 2020. A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine. Journal of Pharmacy and Pharmacology, 72(10), pp.1352-1360.
  3. Verhoork, S.J., Jennings, C.E., Rozatian, N., Reeks, J., Meng, J., Corlett, E.K., Bunglawala, F., Noble, M.E., Leach, A.G. and Coxon, C.R., 2018. Tuning the binding affinity and selectivity of perfluoroaryl-stapled peptides by cysteine-editing. Chemistry-A European Journal, 25(1), pp.177-182.
  4. Verhoork, S.J., Killoran, P.M. and Coxon, C.R., 2018. Fluorinated prolines as conformational tools and reporters for peptide and protein chemistry. Biochemistry, 57(43), pp.6132-6143.