The University of Southampton

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Phone:: (023) 8059 2187
Email:: Sam.Thompson@southampton.ac.uk

Dr Sam Thompson

Lecturer in Chemical Biology and Medicinal Chemistry

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Dr Sam Thompson joined the School of Chemistry at the University of Southampton in October 2016, as a Lecturer in Chemical Biology and Medicinal Chemistry. His main research area is the use of organic synthesis to address problems in biology and medicine – especially those related to proteins.

Sam Thompson grew up in Lincolnshire and received his MChem from Exeter College, Oxford (2004) spending the final year with Prof. Ben Davis FRS in the historic Dyson Perrins Laboratory. He moved to St Edmund’s College, Cambridge for a PhD (2008) with Dr Martin Smith working on: (i) cascade routes to polycyclic alkaloids; and (ii) enantioselective carbon-carbon bond formation under phase-transfer catalysis. Returning to Oxford in 2009 he did a short medicinal chemistry postdoc sponsored by CRUK with Profs. Steve Davies and Angela Russell aimed at developing small molecule drugs for cancer targets. Between 2010 and 2016 he held Junior Research Fellowships at Pembroke College and Lady Margaret Hall, and was the team leader for the group of Prof. Andrew Hamilton FRS during his tenure as Vice-Chancellor at Oxford. This work was multidisciplinary – bringing together organic synthesis, supramolecular chemistry, and chemical biology to develop new approaches to mediate therapeutically relevant protein-protein interactions. Sam is also a passionate teacher having held Lectureships at several Oxford colleges, with particularly strong links to Christ Church, Lady Margaret Hall, and Pembroke.

Research

Publications

Contact

Research interests

The inspiration and motivation for research in the group derives from the exquisite control that Nature exerts over structure and function – at both atomic and macromolecular levels. Unmet challenges in biology and medicine stem from gaps in our understanding of the basic science underlying these processes and a shortage of tools for the interrogation and manipulation of specific interactions. Proteins constitute a bio-macromolecular class of particular interest due to their essential roles in all life forms, performing myriad structural, catalytic, and signalling functions. They are critically important in numerous disease states including cancer, diabetes, and neurodegeneration. In this context our major long-term goals are to develop a deeper understanding of the structure/function relationships governing therapeutically relevant protein-protein interactions (PPIs) and protein-misfolding conditions, and to develop molecular tools for their manipulation. In our group organic synthesis and methodology are central tools allied with rigorous structural and conformational assignment by solution- and solid-phase methods (especially NMR and X-ray). Combined with techniques from the fields of supramolecular chemistry, physical organic, and chemical biology this makes for multi-disciplinary projects. We have established collaborations with experts in molecular- and cellular-biology, providing insights into the behaviour of our chemical probes in physiologically relevant settings. Recent work in our lab has focussed on the rational design of non-peptidic conformationally preorganised scaffolds that mimic key recognition elements of protein surfaces. These peptidomimetics have shown efficacy in mediating therapeutically relevant PPIs and intrinsically disordered proteins, including cancer and type II diabetes. Current work is focused on expanding this molecular toolkit for the recognition, interrogation, and regulation of disparate protein targets, including those implicated in ageing and neurodegeneration such as Alzheimer’s, Parkinson’s, and prion conditions.

Research group

Chemical Biology, Diagnostics and Therapeutics

Key Publications

Peacock, H., Luo, J., Yamashita, T., Luccarelli, J., Thompson, S., & Hamilton, A. D. (2016). Non-covalent S...O interactions control conformation in a scaffold that disrupts islet amyloid polypeptide fibrillation. Chemical Science, 7(10), 6435-6439. DOI: 10.1039/c6sc00756b, 10.1039/C6SC00756B

German, E. A., Ross, J. E., Knipe, P. C., Don, M. F., Thompson, S., & Hamilton, A. D. (2015). B-strand mimetic foldamers rigidified through dipolar repulsion. Angewandte Chemie International Edition, 54(9), 2649-2652. DOI: 10.1002/anie.201410290

Lingard, H., Han, J. T., Thompson, A. L., Leung, I. K. H., Scott, R. T. W., Thompson, S., & Hamilton, A. D. (2014). Diphenylacetylene-linked peptide strands induce bidirectional B-sheet formation. Angewandte Chemie International Edition, 53(14), 3650-3653. DOI: 10.1002/anie.201309353

Sutherell, C. L., Thompson, S., Scott, R. T. W., & Hamilton, A. D. (2012). Aryl-linked imidazolidin-2-ones as non-peptidic beta-strand mimetics. Chemical Communications, 48(79), 9834-9836. DOI: 10.1039/C2CC34791A

Maciver, E. E., Thompson, S., & Smith, M. D. (2009). Catalytic asymmetric 6pi electrocyclization: enantioselective synthesis of functionalized indolines. Angewandte Chemie International Edition, 48(52), 9979-9982. DOI: 10.1002/anie.200905169

Bernardes, G. J. L., Grayson, E. J., Thompson, S., Chalker, J. M., Errey, J. C., El Oualid, F., ... Davis, B. G. (2008). From disulfide- to thioether-linked glycoproteins. Angewandte Chemie International Edition, 47(12), 2244-2247. DOI: 10.1002/anie.200704381

Articles

Busschaert, N., Thompson, S., & Hamilton, A. D. (2017). An alpha-helical peptidomimetic scaffold for dynamic combinatorial library formation. Chemical Communications, 53(2), 313-316. DOI: 10.1039/C6CC07787K

Knipe, P. C., Thompson, S., & Hamilton, A. D. (2016). Acid-mediated topological control in a functionalized foldamer. Chemical Communications, 52(39), 6521-6524. DOI: 10.1039/C6CC01496H

Thompson, S. (2016). Inside back cover. Chemical Communications, 52(39), 6627-6627. DOI: 10.1039/C6CC90207C

Peacock, H., Luo, J., Yamashita, T., Luccarelli, J., Thompson, S., & Hamilton, A. D. (2016). Non-covalent S...O interactions control conformation in a scaffold that disrupts islet amyloid polypeptide fibrillation. Chemical Science, 7(10), 6435-6439. DOI: 10.1039/c6sc00756b, 10.1039/C6SC00756B

Yamashita, T., Knipe, P. C., Busschaert, N., Thompson, S., & Hamilton, A. D. (2015). A Modular Synthesis of Conformationally Preorganised Extended β-Strand Peptidomimetics. Chemistry - A European Journal, 21(42), 14699-14702. DOI: 10.1002/chem.201501366

Kulikov, O. V., Kumar, S., Magzoub, M., Knipe, P. C., Saraogi, I., Thompson, S., ... Hamilton, A. D. (2015). Amphiphilic oligoamide a-helix peptidomimetics inhibit islet amyloid polypeptide aggregation. Tetrahedron Letters, 56(23), 3670-3673. DOI: 10.1016/j.tetlet.2015.02.132

German, E. A., Ross, J. E., Knipe, P. C., Don, M. F., Thompson, S., & Hamilton, A. D. (2015). B-strand mimetic foldamers rigidified through dipolar repulsion. Angewandte Chemie International Edition, 54(9), 2649-2652. DOI: 10.1002/anie.201410290

Yamashita, T., Knipe, P. C., Busschaert, N., Thompson, S., & Hamilton, A. D. (2015). Cover picture: a modular synthesis of conformationally preorganised extended B-strand peptidomimetics (Chem. Eur.J. 42/2015). Chemistry - A European Journal, 21(42), 14653-14653. DOI: 10.1002/chem.201584201

Ross, J. E., Knipe, P. C., Thompson, S., & Hamilton, A. D. (2015). Hybrid diphenylalkyne-dipeptide oligomers induce multistrand B-sheet formation. Chemistry - A European Journal, 21(39), 13518-13521. DOI: 10.1002/chem.201502690

Jayatunga, M. K. P., Thompson, S., McKee, T. C., Chan, M. C., Reece, K. M., Hardy, A. P., ... Hamilton, A. D. (2015). Inhibition of the HIF1a-p300 interaction by quinone- and indandione-mediated ejection of structural Zn(II). European Journal of Medicinal Chemistry, 94, 509-516. DOI: 10.1016/j.ejmech.2014.06.006

Knipe, P. C., Thompson, S., & Hamilton, A. D. (2015). Ion-mediated conformational switches. Chemical Science, 6(3), 1630-1639. DOI: 10.1039/C4SC03525A

Knipe, P. C., Lingard, H., Jones, I. M., Thompson, S., & Hamilton, A. D. (2014). A Lewis acid-mediated conformational switch. Organic & Biomolecular Chemistry, 12(40), 7937-7941. DOI: 10.1039/C4OB01556H

Jayatunga, M. K. P., Thompson, S., & Hamilton, A. D. (2014). a-helix mimetics: outwards and upwards. Bio-organic & Medicinal Chemistry Letters, 24(3), 717-724. DOI: 10.1016/j.bmcl.2013.12.003

Lingard, H., Han, J. T., Thompson, A. L., Leung, I. K. H., Scott, R. T. W., Thompson, S., & Hamilton, A. D. (2014). Cover picture: diphenylacetylene-linked peptide strands induce bidirectional B-sheet formation (Angew. Chem. Int. Ed. 14/2014). Angewandte Chemie International Edition, 53(14), 3521-3521. DOI: 10.1002/anie.201401099

Lingard, H., Han, J. T., Thompson, A. L., Leung, I. K. H., Scott, R. T. W., Thompson, S., & Hamilton, A. D. (2014). Diphenylacetylene-linked peptide strands induce bidirectional B-sheet formation. Angewandte Chemie International Edition, 53(14), 3650-3653. DOI: 10.1002/anie.201309353

Jones, I., Knipe, P., Michaelos, T., Thompson, S., & Hamilton, A. (2014). Redox-dependent conformational switching of diphenylacetylenes. Molecules, 19(8), 11316-11332. DOI: 10.3390/molecules190811316

Knipe, P. C., Jones, I. M., Thompson, S., & Hamilton, A. D. (2014). Remote conformational control of a molecular switch via methylation and deprotonation. Organic & Biomolecular Chemistry, 12(46), 9384-9388. DOI: 10.1039/C4OB01991A

Egleton, J. E., Thinnes, C. C., Seden, P. T., Laurieri, N., Lee, S. P., Hadavizadeh, K. S., ... Russell, A. J. (2014). Structure–activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1. Bioorganic & Medicinal Chemistry, 22(11), 3030-3054. DOI: 10.1016/j.bmc.2014.03.015

Aziz, S. A., Laurieri, N., Egleton, J. E., Varney, A., Thinnes, C. C., Quevedo, C. E., ... Sim, E. (2013). A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1. PLoS ONE, 8(8), 1-6. DOI: 10.1371/journal.pone.0070600

Kulikov, O. V., Thompson, S., Xu, H., Incarvito, C. D., Scott, R. T. W., Saraogi, I., ... Hamilton, A. D. (2013). Design and synthesis of oligoamide-based double a-helix mimetics. European Journal of Organic Chemistry, 2013(17), 3433-3445. DOI: 10.1002/ejoc.201300363

Kulikov, O. V., Thompson, S., Xu, H., Incarvito, C. D., Scott, R. T. W., Saraogi, I., ... Hamilton, A. D. (2013). Design and synthesis of oligoamide-based double a-helix mimetics (Eur. J. Org. Chem. 17/2013). European Journal of Organic Chemistry, 2013(17). DOI: 10.1002/ejoc.201390045

Thompson, S., Wilson, A. J., & Battersby, A. R. (2013). In celebration of the 60th birthday of Professor Andrew D. Hamilton FRS. Organic & Biomolecular Chemistry, 11(37), 6236-6241. DOI: 10.1039/C3OB90109B

Simister, P. C., Luccarelli, J., Thompson, S., Appella, D. H., Feller, S. M., & Hamilton, A. D. (2013). Novel inhibitors of a Grb2 SH3C domain interaction identified by a virtual screen. Bioorganic & Medicinal Chemistry, 21(14), 4027-4033. DOI: 10.1016/j.bmc.2012.10.023

Nevola, L., Rodriguez, J. M., Thompson, S., & Hamilton, A. D. (2013). Super-secondary structure peptidomimetics: design and synthesis of an a–a hairpin analogue. Supramolecular Chemistry, 25(9-11), 586-590. DOI: 10.1080/10610278.2013.817581

Thompson, S., & Hamilton, A. D. (2012). Amphiphilic a-helix mimetics based on a benzoylurea scaffold. Organic & Biomolecular Chemistry, 10(30), 5780-5782. DOI: 10.1039/C2OB25273B

Sutherell, C. L., Thompson, S., Scott, R. T. W., & Hamilton, A. D. (2012). Aryl-linked imidazolidin-2-ones as non-peptidic beta-strand mimetics. Chemical Communications, 48(79), 9834-9836. DOI: 10.1039/C2CC34791A

Thompson, S., Vallinayagam, R., Adler, M. J., Scott, R. T. W., & Hamilton, A. D. (2012). Double-sided a-helix mimetics. Tetrahedron, 68(23), 4501-4505. DOI: 10.1016/j.tet.2011.11.010

Maciver, E. E., Thompson, S., & Smith, M. D. (2009). Catalytic asymmetric 6pi electrocyclization: enantioselective synthesis of functionalized indolines. Angewandte Chemie International Edition, 48(52), 9979-9982. DOI: 10.1002/anie.200905169

Bernardes, G. J. L., Grayson, E. J., Thompson, S., Chalker, J. M., Errey, J. C., El Oualid, F., ... Davis, B. G. (2008). From disulfide- to thioether-linked glycoproteins. Angewandte Chemie International Edition, 47(12), 2244-2247. DOI: 10.1002/anie.200704381

Letter/Editorial

Yamashita, T., Knipe, P. C., Busschaert, N., Thompson, S., & Hamilton, A. D. (2015). A Modular Synthesis of Conformationally Preorganised Extended β-Strand Peptidomimetics (Cover profile). Chemistry - A European Journal, 21(42), 14657. DOI: 10.1002/chem.201503218

Book Chapters

Knipe, P. C., Thompson, S., & Hamilton, A. D. (2016). Molecular recognition in biomimetic receptors. In R. M. Izatt (Ed.), Macrocyclic and Supramolecular Chemistry: How Izatt–Christensen Award Winners Shaped the Field. (pp. 146-164). Chichester, GB: John Wiley & Sons. DOI: 10.1002/9781119053859.ch7

Luccarelli, J., Thompson, S., & Hamilton, A. D. (2013). SH3 domains as drug targets. In A. Domling (Ed.), Protein-Protein Interactions in Drug Discovery. (pp. 101-128). (Methods and Principles in Medicinal Chemistry). Weinheim, DE: Wiley-VCH Verlag GmbH & Co. DOI: 10.1002/9783527648207.ch6

Dr Sam Thompson
Chemistry University of Southampton Highfield Southampton SO17 1BJ

Room Number:30/4041

Telephone:(023) 8059 2187
Email:Sam.Thompson@southampton.ac.uk

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