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Staff Profile

Dr Steven Cobb

Personal web page

Senior Lecturer in the Department of Chemistry
Telephone: +44 (0) 191 33 42086

(email at s.l.cobb@durham.ac.uk)

Biography

Steven Cobb carried out his PhD with Professor David O’Hagan at St. Andrews University (2001-2005). His work focused on the biosynthesis of fluorinated natural products, in the bacteria Streptomyces cattleya. The highlight of this research was the identification of the first ever naturally-occurring C-F bond forming enzyme (Nature, 2002, 416, 279). Steven was awarded an Alberta Heritage Foundation for Medical Research Fellowship and moved to the University of Alberta, to work with Professor John Vederas, FRS. During this time he was introduced to the field of peptide chemistry and he worked on the development of new peptide based antibiotics. In October 2007 Steven moved to the Chemistry Department at Durham University as a temporary lecturer, and from this position he was awarded a prestigious Ramsay Memorial Trust Research Fellowship (2008–2010). In 2010 he was appointed to the position of Lecturer and since then he has attracted research funding from various competitive sources as a PI including the Royal Society, the EPSRC, The Wellcome Trust, The Leverhulme Trust, UK industry and he was recently the successful PI on a Bill and Melinda Gates Foundation Grant (one of only 100 grants award worldwide from over 2100 applications).

Research Interests

Our group uses a range of methods and techniques in synthetic organic and peptide chemistry to tackle interesting and challenging biological problems.

Some project highlights include:

New antiparasitics inspired by naturally occurring antimicrobial peptides are being developed in collaboration with researchers both at Durham (Dr Paul Denny) and at the Walter Reed Army Institute of Medical Research (Maryland, US).

Working with Dr Ehmke Pohl (Durham, Protein Crystallography) and Professors Simi Ali and John Kirby (Newcastle University, Medical School) peptide inhibitors of chemokine induced chemotaxis are being designed, with the aim of reducing inflammation and thus protecting cardiac tissue during heart by-pass operations.

New biomaterials and light activated peptide drug delivery systems that exploit novel amino acids prepared in the group are being developed in collaboration with Dr Karl Coleman (Durham) and Dr Ka-La Wong (Hong Kong Baptist University) respectively.

Utilising Solid Phase Peptide Synthesis (SPPS) novel amino acids probes prepared within the group are being incorporated site specifically in small proteins (up to 200 amino acids in size). The incorporation of these novel amino acids provides a reactive handle for selective and controlled protein modification or they enable information about a specific protein to be gathered using a range of biophysical techniques. At the present time we are carrying out the total chemical synthesis of several targets with the aim of providing labelled proteins that can be used as to understand things such as protein-protein interactions and protein misfolding in a range of diseases.

For further details, see my personal web pages

Selected Publications

  • Li H., Chadbourne FL, Lan R., Chi-Fai Chan, Wai-Lun Chan W-L, Law G-L,* Chi-Sing Lee,* Cobb SL, and Wong K-L*Structural and functional analysis of lanthanide bioprobes for europium signaling changes in different Cyclin A concentrations on living tumor cells. 2013, Dalton Trans. DOI: 10.1039/C3DT51053K
  • Hudson AS., Hoose A, Coxon CR.,Sandford G. and Cobb SL, Synthesis of a novel tetrafluoropyridine containing amino acid and tripeptide. Tetrahedron Lett. 2013, 54(36), 4865-4867
  • Saleki M, Colgin N, Kirby JA, Cobb SL and Ali S. Evaluation of two cyclic di-peptides as inhibitors of CCL2 induced chemotaxis. Med. Chem. Comm., 2013, 4, 860-864
  • Colgin N, Tatum NJ, Pohl E, Cobb SL, G. Sandford. Synthesis and molecular structure of a perfluorinated pyridyl carbanion. J. Fluorine Chem. 2012, 133, 33-37 
  • Colgin N, Flinn T, Cobb SL. Synthesis and properties of MIDA boronate containing aromatic amino acids: New peptide building blocks. Org. Biomol. Chem. 2011, 9, 1864 – 1870.
  • Kong HK, Chadbourne FL, Law GL, Ko CYT, Tam HL, Cobb SL, Lau CK, Lee CS, Wong KL. Two-Photon Induced Responsive f-f Emissive Detection for Cyclin A with Europium-Chelating Peptide. Chem. Commun., 2011, 47, 8052-8054.
  • Chadbourne FL, Raleigh C, Ali HZ, Denny PW, Cobb SL, Studies on the antileishmanial properties of the antimicrobial peptides Temporin A, B and 1Sa. J. Pept. Sci. 2011, 17, 751-755

Research Groups

Department of Chemistry

  • Bioactive Chemistry and Synthesis
  • Functional Molecules and Materials

Wolfson Research Institute for Health and Wellbeing

Research Interests

  • Peptide Drug Design and Delivery
  • Peptidomimetics
  • Bioorganic Fluorine Chemistry

Publications

  • 1: Cobb, S.L. & Murphy, C.D. (2009). 19F NMR applications in chemical biology. Journal of Fluorine Chemistry 130(2): 132-143.
  • 2: Cobb, S.L. & Denny, P.W. (2010). Antimicrobial peptides for leishmaniasis. Current Opinion in Investigational Drugs 11(8): 868-875.
  • 3: Kong, H.K., Chadbourne, F.L., Law, G.L., Li, H., Tam, H.L., Cobb, S.L., Lau, C.K., Lee, C.S. & Wong, K.L. (2011). Two-photon induced responsive f–f emissive detection of Cyclin A with a europium-chelating peptide. Chemical Communications 47(28): 8052-8054.
  • 4: Colgin, N., Flinn, T. & Cobb, S.L. (2011). Synthesis and properties of MIDA boronate containing aromatic amino acids: New peptide building blocks. Organic & Biomolecular Chemistry 9(6): 1864-1870.
  • 5: Chadbourne, F.L., Raleigh, C., Ali, H.Z., Denny, P.W. & Cobb, S.L. (2011). Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa. Journal of Peptide Science 17(11): 751-755.
  • 6: Colgin, N., Tatum, N.J., Pohl, E., Cobb, S.L. & Sandford, G. (2012). Synthesis and molecular structure of a perfluorinated pyridyl carbanion. Journal of Fluorine Chemistry 133: 33-37.
  • 7: Hudson, A., Hoose, A., Sandford, G. & Cobb, S.L. (2013). Synthesis of a novel tetra-fluoropyridine containing amino acid and tripeptide. Tetrahedron Letters 54(36): 4865-4867.
  • 8: Li, H., Chadbourne, F.L., Lan, R., Chan, C.F., Chan, W.L., Law, G.L., Lee, C.S., Cobb, S.L. & Wong, K.L. (2013). Real time detection of cell cycle regulator cyclin A on living tumor cells with europium emission. Dalton Transactions 42(37): 13495-13501.
  • 9: Saleki, M., Colgin, N., Kirby, J.A., Cobb, S.L. & Ali, S. (2013). Evaluation of two cyclic di-peptides as inhibitors of CCL2 induced chemotaxis. MedChemComm 4(5): 860-864.
  • 10: West, C.W., Hudson, A.S., Cobb, S.L. & Verlet, J.R.R. (2013). Communication: Autodetachment versus internal conversion from the S1 state of the isolated GFP chromophore anion. The Journal of Chemical Physics 139(7): 071104.
  • 11: Trmčić, M., Chadbourne, F.L., Brear, P.M., Denny, P.W., Cobb, S.L. & Hodgson, D.R.W. (2013). Aqueous synthesis of N,S,-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. Organic and Biomolecular Chemistry 11(16): 2660-2675.
  • 12: O’Connor, N.K., Hudson, A.S., Cobb, S.L., O’Neil, D., Robertson, J., Duncan, V. & Murphy, C.D. (2014). Novel fluorinated lipopeptides from Bacillus sp. CS93 via precursor-directed biosynthesis. Amino Acids 46(12): 2745-2752.
  • 13: Li, H., Chan, C.F., Chan, W.L., Lear, S., Cobb, S.L., Mak, N.K., Lau, T.C., Lan, R., Wong, W.K. & Wong, K.L. (2014). Monitoring and inhibition of Plk1: amphiphilic porphyrin conjugated Plk1 specific peptides for its imaging and anti-tumor function. Organic & Biomolecular Chemistry 12(31): 5876-5882.
  • 14: Foster, J. A., Edkins, R. M., Cameron, G. J., Colgin, N., Fucke, K., Ridgeway, S., Crawford, A. G., Marder, T. B., Beeby, A., Cobb, S. L. & Steed, J. W. (2014). Blending gelators to tune gel properties and probe anion-induced disassembly. Chemistry - A European Journal 20(1): 279-291.
  • 15: Chan, C.-F., Tsang, M.-K., Li, H., Lan, R., Chadbourne, F.L. , Chan, W.-L., Law, G.-L., Cobb, S.L., Hao, J., Wong, W.-T. & Wong, K.-L. (2014). Bifunctional up-converting lanthanide nanoparticles for selective in vitro imaging and inhibition of cyclin D as anti-cancer agents. Journal of Materials Chemistry B 2(1): 84-91.
  • 16: Webster, Alexandra M. , Coxon, Christopher R., Kenwright, Alan M., Sandford, Graham & Cobb, Steven L. (2014). A mild method for the synthesis of a novel dehydrobutyrine-containing amino acid. Tetrahedron 70(31): 4661-4667.
  • 17: Eggimann, G.A., Bolt, H.L., Denny, P.W. & Cobb, S.L. (2015). Investigating the Anti-leishmanial Effects of Linear Peptoids. ChemMedChem 10(3): 233-237.
  • 18: Hudson, A.S., Caron, L., Colgin, N. & Cobb, S.L. (2015). A direct method for the synthesis of orthogonally protected furyl and thienyl amino acids. Amino Acids 47(4): 779-785.
  • 19: Eggimann, G.A., Sweeney, K., Bolt, H.L., Rozatian, N., Cobb, S.L. & Denny, P.W. (2015). The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides. Molecules 20(2): 2775-2785.
  • 20: Tatum, N.J., Yufit, D.S., Cobb, S.L. & Coxon, C.R. (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.
  • Gimenez, D., Dose, A., Robson, N.L., Sandford, G., Cobb, S.L. & Coxon, C.R. (2017). 2,2,2-Trifluoroethanol as a Tool to Control Nucleophilic Peptide Arylation. Organic and Biomolecular Chemistry 15(19): 4081-4085.
  • Bolt, Hannah L., Eggimann, Gabriela A., Jahoda, Colin A.B., Zuckermann, Ronald N., Sharples, Gary J. & Cobb, Steven L. (2017). Exploring the links between peptoid antibacterial activity and toxicity. Medicinal Chemical Communications 8(5): 886-896.
  • Bolt, H. L., Williams, C. E. J., Brooks, R. V., Zuckermann, R. N., Cobb, S. L. & Bromley, E. H. C. (2017). Log D versus HPLC derived hydrophobicity: The development of predictive tools to aid in the rational design of bioactive peptoids. Peptide Science 108(4): e23014.
  • Luoa, Y., Bolt, H.L., Eggimann, G.A., McAuley, D.F., McMullan, R., Curran, T., Zhoud, M., Jahoda, C.A.B., Cobb, S.L. & Lundy, F.T. (2017). Peptoid efficacy against polymicrobial biofilms determined using propidium monoazide-modified quantitative PCR. ChemBioChem 18(1): 111-118.
  • Webster, Alexandra M. & Cobb, Steven L. (2017). Synthesis of Biaryl-Linked Cyclic Peptoids. Tetrahedron Letters 58(10): 1010-1014.
  • Gimenez, D., Mooney, C.A., Dose, A., Sandford, G., Coxon, C.R. & Cobb, S.L. (2017). The Application of Perfluoroheteroaromatic Reagents in the Preparation of Modified Peptide Systems. Organic and Biomolecular Chemistry 15(19): 4086-4095.
  • Bolt, H.L. & Cobb, S.L. (2016). A practical method for the synthesis of peptoids containing both lysine-type and arginine-type monomers. Organic and Biomolecular Chemistry 14(4): 1211-1215.
  • Bolt, H.L., Denny, P.W. & Cobb, S.L. (2016). An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity. Journal of Visualized Experiments 117: e54750.
  • Jiang, L., Lan, R., Huang, T., Chan, C., Li, H., Lear, S., Zong, J., Wong, W., Lee, M.M., Chan, B.D., Chan, W., Lo, W., Mak, N., Lung, M.L., Tsao, S.W., Taylor, G.S., Bian, Z., Tai, W.C.S., Law, G., Wong, W.T., Cobb, S.L. & Wong, K.L. (2016). EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein–Barr virus. Nature Biomedical Engineering 1: 0042
  • Bolt, H.L., Eggimann, G.A., Denny, P.W. & Cobb, S.L. (2016). Enlarging the chemical space of anti-leishmanials: a structure-activity relationship study of peptoids against Leishmania mexicana, a causative agent of cutaneous leishmaniasis. Medicinal Chemistry Communications 7(5): 799-805.
  • Lear, S. & Cobb, S.L. (2016). Pep-Calc.com: a set of web utilities for the calculation of peptide and peptoid properties and automatic mass spectral peak assignment. Journal of Computer-Aided Molecular Design 30(3): 271-277.
  • Lear, S., Munshi, T., Hudson, A.S., Hatton, C., Clardy, J., Mosely, J.A., Bull, T.J., Sit, C.S. & Cobb, S.L. (2016). Total Chemical Synthesis of Lassomycin and Lassomycin-Amide. Organic and Biomolecular Chemistry 14(19): 4534-4541.

Supervises