Paul Teesdale Spittle
PhD, University of Nottingham, UK | BSc (Hons), University of Nottingham, UK
Having completed a BSc(Hons) in Chemistry at Nottingham University in the UK, I found myself completing a PhD in peptide chemistry. From there, I took up a position teaching organic chemistry, but found myself progressively more interested in the chemical principles underpinning biology. Chemistry for the sake of chemistry became chemistry for the sake of biology. Then it became how chemistry can inform biology. Now I work at the interface of biology and chemistry, looking at how drug-like molecules interact with biological systems (using some of the tools of cellular and systems biology) and developing new versions of bioactive compounds (using the tools of organic chemistry).
My research is primarily focused on the biological evaluation of compounds for the treatment of cancer, coupled to development of new bioactive compounds using chemical techniques.
Current projects are based on the activity of two powerfully active marine natural products, isolated from Mycale sp sponges off the coast of New Zealand. Pateamine interacts with the machinery of protein biosynthesis and has application as an anticancer agent and also in prevention of complex conditions such as the muscle-wasting disease, cachexia. Peloruside stabilises microtubules and so interferes with the processes of cell division. This also makes it an attractive anticancer agent. In both cases we are developing new versions of the compound through synthetic chemistry. These new versions are designed to have refined biological activity coupled to a structure that will allow them to be synthesised at large scale as drugs. An active thread of current research is understanding the impact that pateamine has on the proteome of treated cells. We have additional projects underway on compounds that are selective kinase inhibitors and that interfere with protein trafficking.
A.M Campbell, E.Liebau, J. Barrett, P.M. Brophy, P.H. Teesdale-Spittle and M. Wang. Towards validation of glutathione S-transferase as a nematode drug target. Chem.-Biol. Interact. 2001, 133, 240-243.
Gaitanos TN, Buey RM, Diaz JF, Northcote PT, Teesdale-Spittle P, Andreu JM, Miller JH. Peloruside A does not bind to the taxoid site on beta-tubulin and retains its activity in multidrug-resistant cell lines. Cancer Research 2004, 64, 5063-5067.
Bordeleau ME, Matthews J, Wojnar JM, Lindqvist L, Novac O, Jankowsky E, Sonenberg N, Northcote P, Teesdale-Spittle P, Pelletier J. Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation. Proc. Natl. Acad. Sci U.S.A. 2005, 102,10460-10465.
Casey E.M., Teesdale-Spittle P. and Harvey J.E. Synthesis of the C12-C24 fragment of peloruside A by silyl-tethered diastereomer-discriminating RCM. Tetrahedron Lett 2008, 49, 7021–7023.
Batchelor R, Harvey JE, Northcote PT, Teesdale-Spittle P, and Hoberg JO. Heptanosides from Galactose-Derived Oxepenes via Stereoselective Addition Reactions. J. Org. Chem. 2009, 74, 7627–7632.