... understanding life in molecular detail

Prof Bruce Turnbull

Chemical Biology, Protein-sugar interactions, Protein modification


My research interests range from developing new chemical and enzymatic methods for  protein modification and synthesising carbohydrates with the aim to studying carbohydrate-binding proteins and their applications in synthetic biology.

Current major projects include:
  • Re-engineering proteins for synthetic biology/drug delivery
  • Bacterial toxins that interact with cell surface carbohydrates
  • Site-specific chemical and enzymatic modification of proteins
  • chemical and enzymatic carbohydrate synthesis

Bacterial toxins that interact with cell surface carbohydrates

Protein toxins that are produced by bacteria are a major cause of diarrhoeal disease. We are studying a family of AB5 protein toxins that comprise a single toxic A-subunit that is linked to a non-toxic pentamer of B-subunits that can bind to glycolipids on a cell surface prior to endocytosis of the toxin. We use a range of biophysical methods (ITC, AUC, AFM, DLS) to study these proteins and their interactions with both natural oligosaccharides and synthetic inhibitors.

Site-specific chemical and enzymatic modification of proteins

Modifying proteins with non-peptidic groups (e.g., fluorophores or PEG) can provide useful tools for biochemical/biophysical experiments and also alter protein properties for therapeutic purposes. Traditional methods for protein derivatisation are not always selective and frequently create mixtures of products. We have implemented several methods for the site-specific modification of proteins, and we are developing improved methods for both chemical and enzymatic ligations, e.g.,  sortase-mediated ligation.

Re-engineering proteins for synthetic biology/drug delivery applications

Modern methods for gene synthesis have enabled the growth of synthetic biology in which biological molecules can be thought of as nanoscale building blocks for constructing artificial systems that can interact with living cells. We are exploiting both genetic engineering and the protein modification methods mentioned above to create novel protein capsules and drug delivery vehicles.

Synthetic and mechanistic carbohydrate chemistry

As glycosylation is a post-translational modification, many aspects of gycobiology cannot be studied by standard molecular biology methods. Instead we need synthetic carbohydrates that are well defined and suitable for further functionalisation. We are interested in developing new methods for carbohydrate synthesis which often also requires a detailed understanding of the chemical mechanisms involved. For example, we have introduced a family of bicyclic carbohydrate derivatives that allow us to control the stereoselectivity of the glycosylation reactions.

 

Detailed research programme                  Close ▲
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Chair in Biomolecular Chemistry (2016-Present)
BSc (St.Andrews) PhD (St.Andrews)
RSC Carbohydrate Chemistry Award 2013

PhD in Chemistry (St. Andrews, 1995-98)
Wellcome Trust IPTRF and PDRA (UCLA, 1998-2001; Leeds, 2001-04)
Royal Society University Research Fellow (Leeds, 2005-13)
Associate Professor (2013-Present)

Chemistry G.14
School of Chemistry
0113 343 7438
w.b.turnbull@leeds.ac.uk

http://www.chem.leeds.ac.uk/People/Turnbull.html

Selected Publications

  1. Y. Guo, C. Sakonsinsiri, I. Nehlmeier, M. A. Fascione, H. Zhang, W. Wang, S. Pöhlmann, W. B. Turnbull, D. Zhou, Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent Protein–Ligand Interactions, Angew. Chem., Int. Ed. 2016, 55, 4738-4742. 

  2. T. R. Branson, T. E. McAllister, J. Garcia-Hartjes, M. A. Fascione, J. F. Ross, S. L. Warriner, T. Wennekes, H. Zuilhof, W. B. Turnbull, A Protein-Based Pentavalent Inhibitor of the Cholera Toxin B-Subunit, Angew. Chem., Int. Ed. 2014, 53, 8323-8327.

  3. D. J. Williamson, M. A. Fascione, M. E. Webb and W. B. Turnbull, Efficient N-terminal labeling of proteins by use of sortase, Angew. Chem. Int. Ed. 2012, 51, 9377-9380.

  4. P. K. Mandal, T. R. Branson, E. D. Hayes, J. F. Ross, J. A. Gavín, A. H. Daranas and W. B. Turnbull, Towards a structural basis for the relationship between blood group and the severity of El Tor cholera, Angew. Chem.Int. Ed. 2012, 51, 5143-5146.