Liverpool Skylilne

Pharmacy and Biomolecular Sciences

Dr Christopher Coxon

Dr Christopher Coxon

Telephone: 0151 904 6344

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Biography

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BIOGRAPHY:

Christopher Coxon completed a Cancer Research UK funded PhD under the supervision of Professors Roger Griffin and Bernard Golding at the Northern Institute for Cancer Research, Newcastle University (2010). During this time he became involved with the design and synthesis of small molecule modulators of novel anti-cancer targets, specifically kinases and protein-protein interactions that are pivotal in oncogenic signaling.

Christopher 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. In Oct 2012 he joined Dr Steven Cobb’s group as a senior PDRA, where he investigated routes to multicyclic peptides for application as protein-protein interaction inhibitors; as well as exploring the diverse chemistry of polyfluorinated (hetero)aromatics.

In 2013 Christopher began his independent research career as a temporary lecturer at Durham University, before being appointed to the position of Lecturer in Medicinal and Natural Products Chemistry at Liverpool John Moores University in October 2014.

RESEARCH INTERESTS:

The themes underpinning our groups interests are of a multidisciplinary nature and fall broadly under the umbrella of organic and biological chemistry. We are specifically involved in the synthesis and application of chemical probes to understand complex biological problems and to unravel the key processes involved in diseases typically associated with ageing, including cancer, Alzheimer’s and inflammation. As such, we are developing novel tools to understand cellular signaling through protein-protein interactions (PPIs).

My research interests encompass a wide range of areas including synthetic organic chemistry and peptide chemistry to chemical biology. Specifically, my research focuses on the following areas:

a) Investigating new methodologies for the modification and functionalization of peptide side chains.
b) Investigating and utilising fluorine as a tool for chemical biology and controlling molecular conformation in the context of medicine and catalysis.
c) The synthesis of peptide and small molecule chemical tools to probe diseases e.g. cancer, with a view to developing new treatments.

Each of these strands are applied to the design and synthesis of cell-stable and deliverable peptides and peptide mimetics (stapled peptides, cyclic peptides and peptoids) in targeted drug discovery programmes. Current areas of research include:

a) Cancer – targeting the p53-MDM2 protein-protein interaction (collaboration with Prof. Martin Noble, Newcastle University)
b) Skeletal muscle regeneration and the effects of ageing (collaboration with Dr Adam Sharples, SES, LJMU)
c) Inflammation and the role of neutraceuticals in neuroprotection (collaboration with Dr Darren Sexton, PBS, LJMU)


Anti-Cancer Stapled Peptides

Peptides are a class of therapeutic agent, which have received growing attention in recent years from academia and the pharmaceutical industry alike. They have the potential to treat previously ‘undruggable’ diseases e.g. types of cancer as well as infectious disease and inflammation, as they fill the chemical space between small molecules and large biomacromolecules (e.g. antibodies), combining the advantages of each.

In one project, we are developing alternative technologies for peptide stapling - a method of taking a linear peptide and making it cyclic. This makes peptides resistant to breakdown within a patient, thereby making them more effective medicines and leading to new ways to treat life-threatening and debilitating illnesses. We are using these methods as part of an anti-cancer drug discovery programme aimed at disrupting the p53-MDM2/MDMX protein-protein interaction in collaboration with scientists at the Northern Institute for Cancer Research, Newcastle University.

Degrees

2010, Northern Institute for Cancer Research, Newcastle University, United Kingdom, PhD
2010, Newcastle University, United Kingdom, MChem

Publications

Journal Articles

Gimenez D, Mooney CA, Dose A, Sandford G, Coxon CR, Cobb SL. 2017. The application of perfluoroheteroaromatic reagents in the preparation of modified peptide systems Org. Biomol. Chem., 15 :4086-4095 >DOI

Gimenez D, Dose A, Robson NL, Sandford G, Cobb SL, Coxon CR. 2017. 2,2,2-Trifluoroethanol as a solvent to control nucleophilic peptide arylation Org. Biomol. Chem., 15 :4081-4085 >DOI

Coxon CR, Wong C, Bayliss R, Boxall K, Carr KH, Fry AM, Hardcastle IR, Matheson CJ, Newell DR, Sivaprakasam M, Thomas H, Turner D, Yeoh S, Wang LZ, Griffin RJ, Golding BT, Cano C. 2017. Structure-guided design of purine-based probes for selective Nek2 inhibition Oncotarget, 8 :19089-19124 >DOI

Coxon CR, Anscombe E, Harnor SJ, Martin MP, Carbain B, Golding BT, Hardcastle IR, Harlow LK, Korolchuk S, Matheson CJ, Newell DR, Noble MEM, Sivaprakasam M, Tudhope SJ, Turner DM, Wang LZ, Wedge SR, Wong C, Griffin RJ, Endicott JA, Cano C. 2017. Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines Journal of Medicinal Chemistry, 60 :1746-1767 >DOI

Mitcheson DF, Bottrill AR, Carr K, Coxon CR, Cano C, Golding BT, Griffin RJ, Fry AM, Doerig C, Bayliss R, Tobin AB. 2016. A new tool for the chemical genetic investigation of the Plasmodium falciparum Pfnek-2 NIMA-related kinase Malaria Journal, 15 :1-12 >DOI

Aguilar JA, Ball AT, Coxon CR, Kenwright AM, Lancaster RW, Mosely JA, Mutton MA. 2016. Amorphism and Thermal Decomposition of Salicylsalicylic Acid—A Cautionary Tale Journal of Pharmaceutical Sciences, 105 :3073-3078 >DOI

Tatum NJ, Yufit DS, Cobb SL, Coxon CR. 2015. Synthesis, Ni(II) Schiff base complexation and structural analysis of fluorinated analogs of the ligand (S)-2-[N-(N '-benzylprolyl)amino]benzophenone (BPB) JOURNAL OF FLUORINE CHEMISTRY, 173 :77-83 >DOI >Link

Carbain B, Coxon CR, Lebraud H, Elliott KJ, Matheson CJ, Meschini E, Roberts AR, Turner DM, Wong C, Cano C, Griffin RJ, Hardcastle IR, Golding BT. 2014. Trifluoroacetic acid in 2,2,2-trifluoroethanol facilitates S(N)Ar reactions of heterocycles with arylamines Chemistry (Weinheim an der Bergstrasse, Germany), 20 :2311-2317 >DOI

Webster AM, Coxon CR, Kenwright AM, Sandford G, Cobb SL. 2014. A mild method for the synthesis of a novel dehydrobutyrine-containing amino acid TETRAHEDRON, 70 :4661-4667 >DOI >Link

Carbain B, Coxon CR, Lebraud H, Elliott KJ, Matheson CJ, Meschini E, Roberts AR, Turner DM, Wong C, Cano C, Griffin RJ, Hardcastle IR, Golding BT. 2014. Trifluoroacetic acid in 2,2,2-trifluoroethanol facilitates SNAr reactions of heterocycles with arylamines Chemistry - A European Journal, 20 :2311-2317 >DOI

Lebraud H, Coxon CR, Archard VS, Bawn CM, Carbain B, Matheson CJ, Turner DM, Cano C, Griffin RJ, Hardcastle IR, Baisch U, Harrington RW, Golding BT. 2014. Model system for irreversible inhibition of Nek2: Thiol addition to ethynylpurines and related substituted heterocycles Organic and Biomolecular Chemistry, 12 :141-148 >DOI

Hudson AS, Hoose A, Coxon CR, Sandford G, Cobb SL. 2013. Synthesis of a novel tetrafluoropyridine-containing amino acid and tripeptide TETRAHEDRON LETTERS, 54 :4865-4867 >DOI >Link

Cummins I, Wortley DJ, Sabbadin F, He Z, Coxon CR, Straker HE, Sellars JD, Knight K, Edwards L, Hughes D, Kaundun SS, Hutchings SJ, Steel PG, Edwards R. 2013. Key role for a glutathione transferase in multiple-herbicide resistance in grass weeds Proceedings of the National Academy of Sciences of the United States of America, 110 :5812-5817 >DOI

Blackburn TJ, Ahmed S, Coxon CR, Liu J, Lu X, Golding BT, Griffin RJ, Hutton C, Newell DR, Ojo S, Watson AF, Zaytzev A, Zhao Y, Lunec J, Hardcastle IR. 2013. Diaryl- and triaryl-pyrrole derivatives: Inhibitors of the MDM2-p53 and MDMX-p53 protein-protein interactions MedChemComm, 4 :1297-1304 >DOI

Posters

Coxon CR. 2015. Perfluoroaryl-stapled peptides: Inhibitors of the p53-MDM2 protein-protein interaction Royal Society of Chemistry, Organic Division, North West Regional Meeting

Engagement & Impact

Award:

Award title: Innovate UK (Technology Strategy Board) - Biomed Catalyst award (£200k) Co-I

Award title: LJMU Fully-Funded PhD Scholarship in Allied Health DTA

Award title: Faculty of Science PhD Scholarship 2015, Awarding body: Liverpool John Moores University

Award title: Quantitative detection and identification of protein covalent modifications by chemically reactive metabolites (CRMs) via chromatography with fluorescent probes., Awarding body: AstraZeneca open innovation challenge

External collaboration:

URL: https://www.dur.ac.uk/chemistry/staff/profile/?id=5553, Institution: Durham University, Collaborator: Dr Steven Cobb

URL: http://www.ncl.ac.uk/nicr/staff/profile/martin.noble, Institution: Northern Institute for Cancer Research, Newcastle University, Collaborator: Professor Martin E. Noble

Institution: Durham University, Collaborator: Dr Steven L. Cobb

Institution: Northern Institute for Cancer Research, Newcastle University, Collaborator: Professor Martin E. Noble

Fellowships:

Fellowship title: Fellow of the Higher Education Academy, Organisation: Durham University

Other invited event:

Title of event: MERCIA Chemistry meeting, Location: Liverpool John Moores University, Description: Invited to give a research talk

Title of event: 2016 North West Organic Division Regional Meeting, Location: UCLan, Preston, Description: Invited to give a talk on my research

Title of event: Research Seminar, Location: Department of Chemistry, Nottingham Trent University, Description: Invited to give a talk on my research

Title of event: Research Seminar, Location: Department of Chemistry, Loughborough University, Description: Invited to give a talk on my research

Title of event: Research seminar, Location: Bachem UK, Description: Invited talk

Title of event: Royal Society of Chemistry Chemical Biology and Bioorganic Chemistry Group Meeting 2015, Location: Firbush, Loch Tay, Perthshire, Scotland, Description: I presented current research on 'Perfluoroaryl-stapled peptides: Inhibitors of the p53-MDM2 protein-protein interaction'

Title of event: Pharmacy and Biomolecular Sciences Research Seminar, Location: Liverpool John Moores University, Description: Talk entitled: “Application of fluorine chemistry in the development of stapled peptides for drug discovery”

Title of event: RSC North West Organic Division annual meeting, Location: University of Liverpool, Description: Invited to chair a session at the meeting

Title of event: Royal Society of Chemistry Fluorine Group Meeting 2015, Location: Durham University, Description: Invited to give an oral presentation on my research in the area of fluorine chemistry on the back of a paper recently published in J. Fluor. Chem. Title of talk: Synthesis and structural analysis of fluorinated analogues of nickel (II) complexes used in amino acid synthesis.

Title of event: Invited talk for Oundle School Science Society, Location: Oundle School, Peterborough, Description: Invited to give a talk to the senior science society VI form students. My talk was entitled, "The Discovery of New Medicines: From Witchcraft to Magic Bullets."

Title of event: Invited research seminar, Location: Durham University, Description: I was invited to present my recent research with a talk entitled, "Perfluoroaryl-stapled peptides as inhibitors of the p53-MDM2 protein-protein interaction"

Title of event: The Royal Society of Chemistry 2014 George and Christine Sosnovsky Award in Cancer Therapy, Location: Newcastle University, Description: Invited speaker, giving a talk entitled 'Stabilised Peptides as Chemical Tools in Drug Discovery'. http://www.rsc.org/ScienceAndTechnology/Awards/Sosnovsky/

Teaching qualification:

Title of qualification gained: Fellow of the Higher Education Academy