• Edinburgh

    United Kingdom

Accepting PhD Students

PhD projects

Medicinal chemistry and drug discovery using peptides and fluorine chemistry

20132020

Research output per year

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Personal profile

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

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:
 
  • 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 PRESSPaolo Dognini, Patrick M. Killoran, George S. Hanson, Lewis Halsall, Talhat Chaudhry, Zasharatul Islam, Francesca Giuntini and Christopher R. Coxon

 

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:

 

External positions

Director and co-founder of Pepmotec Ltd

1 Feb 2019 → …

Keywords

  • QD Chemistry

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Research Output

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., 22 May 2020, In : RSC Medicinal Chemistry.

Research output: Contribution to journalArticle

Open Access
File
  • A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine

    von Mentzer, B., Russo, A. F., Zhongming, Z., Kuburas, A., Killoran, P. M., D’Aloisio, V., Nizic, L., Capel, V., Kendall, D. A., Coxon, C. R. & Hutcheon, G. A., 25 Jun 2020, In : Journal of Pharmacy and Pharmacology. 9 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • Peptide based drug delivery systems to the brain

    Islam, Y., Leach, A. G., Smith, J., Pluchino, S., Coxon, C. R., Sivakumaran, M., Downing, J., Fatokun, A. A., Teixidò, M. & Ehtezazi, T., 21 May 2020, In : Nano Express. 1, 1, 23 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • Tuning the Binding Affinity and Selectivity of Perfluoroaryl-Stapled Peptides by Cysteine-Editing

    Verhoork, S. J. M., Jennings, C. E., Rozatian, N., Reeks, J., Meng, J., Corlett, E. K., Bunglawala, F., Noble, M. E. M., Leach, A. G. & Coxon, C. R., 2 Jan 2019, In : Chemistry - A European Journal. 25, 1, p. 177-182 6 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • Fluorinated Prolines as Conformational Tools and Reporters for Peptide and Protein Chemistry

    Verhoork, S. J. M., Killoran, P. M. & Coxon, C. R., 30 Oct 2018, In : Biochemistry. 57, 43, p. 6132-6143 12 p.

    Research output: Contribution to journalReview article

    Open Access
    File
  • Prizes

    Vice Chancellor's Medal for Research and Scholarship

    Christopher Coxon (Recipient), 13 Jun 2019

    Prize: Prize (including medals and awards)