Paul Teesdale Spittle
- synthesis and mode of action studies of biologically active molecules; chemical biology; drug-target interactions.
My research is primarily focused on the design, synthesis and evaluation of compounds for the treatment of cancer and parasite infection. To this end, I make use of computational techniques (including molecular modelling of ligand-target interactions and structure activity relationship analysis), chemical synthesis (by solution and solid phase techniques, including parallel combinatorial synthesis), and in vitro assays.
Current projects involve inhibitors of glutathione S-transferase enzymes as antiparasitic agents, peloruside and its analogues and bioreducible anthraquinone N-oxide topoisomerase inhibitors as anticancer agents. I am also interested in understanding and harnessing WW domains, which are associated with protein recognition and binding.
Visit the Chemical Genetics Laboratory web page.
Selection of publications
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.
Singh AJ, Razzak M, Teesdale-Spittle P, Gaitanos TN, Wilmes A, Paterson I, Goodman J, Miller JH, Northcote PT. Structure-activity studies of the pelorusides: new congeners and semi-synthetic analogues. Org. Biomol. Chem. 2011, 9, 4456-4466.