Dr Sarah Rawe
T: (+353-1) 402 4570
F: (+353-1) 402 4989
E: sarah.rawe@dit.ie
MChem PhD (Liverpool)
Profile
Dr. Sarah Rawe completed her PhD at the University of Liverpool on the synthesis and biological evaluation of novel endoperoxide-containing antimalarials under the supervision of Prof. Paul M. O’Neill and Dr. Richard Storr (1999-2003). After a short spell as a research assistant with Dr. Andrew V. Stachulski investigating a new approach for the treatment of neuropathic pain (also at the University of Liverpool) she moved to Ireland. She then worked as a postdoctoral fellow in the Centre for Synthesis and Chemical Biology at UCD (2004-2005, under the supervision of Prof. Paul V. Murphy) investigating carbohydrate-derived inhibitors of angiogenesis before being appointed to her current position as a lecturer in organic and medicinal chemistry in January 2006. She currently supervises 4 postgraduate students. Her pedagogical interests are the integration of research and embedding of research skills in undergraduate education and she is a member of CERT.
Research Interests
Synthesis and Biological Evaluation of Endoperoxide-containing Drug Hybrids
Combination therapies (where a patient receives two or more drugs at the same time) are common but a newer approach is the development of drug hybrids. The hybrid approach involves covalently linking two distinct chemical entities to form a single drug thus allowing simultaneously delivery to tumour cells. In our lab, we have prepared a library of novel hybrids and are currently evaluating them for their antitumour activity.
The work has allowed us to work closely with collaborators from Europe and Ireland including Prof. Paul O’Neill and colleagues at the University of Liverpool, Dr. Ivo Piantanida (Head of the Start-up Laboratory for Study of Interactions of Biomacromolecules, "Ruđer Bošković" Institute, Zagreb, Croatia), Dr. James Murphy (SFI Stokes Lecturer, IT Sligo) and Dr. Orla Howe (RESC, Focas Institute, DIT). The postgraduate students involved in the work have or will spend time in the laboratories of our collaborators.
Synthesis of Heterocycles and Porphyrins
Pyrroles and thiophenes are simple heterocycles with applications in numerous fields including materials science and medicine. Our collaborator (Dr. J. Mike Southern, TCD) has developed and reported a versatile route to uniquely substituted thiophenes, a class of compounds of great interest as organic semiconductors, and together we have now extended this chemistry to produce pyrroles. Our novel pyrroles and thiophenes are building blocks for an even more exciting class of compounds, porphyrins, and we have now turned our attention to their synthesis. Porphyrins (tetrapyrroles) are a unique class of compounds that have functions and applications in a wide variety of roles. We are interested in developing them as PDT agents and investigating their properties as new materials (optics, sensors, molecular wires, catalysis and artificial photosynthesis).
We collaborate with Dr. J. Mike Southern and Prof. Mathias Senge (TCD) on this project and the postgraduate student spends her time between the MSA laboratory in Focas, DIT and the chemistry laboratories in TCD.
Synthesis and Antimicrobial Activity of Glycolipids
Fatty acids have demonstrable antibacterial activity and the goal of this work is to enhance the activity by conjugation to a sugar. We are working with Drs. Julie Dunne, Paula Bourke and co-workers in the School of Food Science and Environmental Health, DIT. We are also investigating the activity of related compounds with Dr. Trinidad Velasco-Torrijos and colleagues at NUI Maynooth.
Research is funded by SFI, IRCSET, Strand I and DIT.
Publications/ Communications
Michael Jones, Amy E. Mercer, Paul A. Stocks, Louise J. I. La Pensée, Rick Cosstick, B. Kevin Park, Miriam E. Kennedy, Ivo Piantanida, Stephen A. Ward, Jill Davies, Patrick G. Bray, Sarah L. Rawe,* Jonathan Baird, Tafadzwa Charidza, Omar Janneh, Paul M. O’Neill* , Antitumour and antimalarial activity of artemisinin–acridine hybrids, Bioorganic and Medicinal Chemistry Letters, 2009, 19(7), 2033. DOI: 10.1016/j.bmcl.2009.02.028
Guillaume Anquetin, Gareth Horgan, Sarah Rawe, David Murray, Aideen Madden, Padraic MacMathuna, Peter Doran, Paul V. Murphy, Synthesis of Novel Macrolactam and Macroketone Analogues of Migrastatin from D-Glucal and Comparison with Macrolactone and Acyclic Analogues: A Dorrigocin A Congener Is a Potent Inhibitor of Gastric Cancer Cell Migration, European Journal of Organic Chemistry, 2008, http://dx.doi.org/10.1002/ejoc.200701192
"Synthesis and Biomimetic Fe(II) Chemistry of Anti-tumor and Antimalarial Peroxides", Chapter 17 in "The Chemistry of Peroxides", edited by Zvi Rappoport, (ISBN 0-470-86274-2), Wiley, April 2006.
Sarah L. Rawe, Kevin McMahon, Evelyn P. Murphy, Paul V. Murphy, Synthesis of Novel Migrastatin and Dorrigocin A Analogues from D-Glucal Guillaume Anquetin, Chemistry - A European Journal 2007, 14 (5), 1592-1600
Sarah L. Rawe, Violeta Zaric, Dearbhla Doyle, Kathy M. O¿Boyle and Paul V. Murphy, N-Glycosylthiophene-2-carboxamides. Effects on growth on diverse cell types in the presence and absence of bFGF. Identification of a per-O-acetylated b-mannopyranoside conjugate with enhanced potency, Carbohydrate Research, 2006, 1370-13
Sarah L. Rawe, Violeta Zaric, Kathy O¿Boyle and Paul V. Murphy, Glycosylthiophene-2-carboxamides. Effects on endothelial cell growth in the presence and absence of bFGF. A significant increase in potency using per-O-acetylated analogues, Bioorganic and Medicinal Chemistry Letters, 2006, 1316-1319.
Sarah L. Rawe and Paul V. Murphy, Structural Analysis of Thiophene Carboxamides Showing Intramolecular NH-Acetylene Interaction, Abstracts of Papers, 230th ACS National Meeting, Washington, DC, United States, Aug 28-1 2005 (2005). Oral Presentation.
Sarah L. Rawe, Violeta Zaric, Dearbhla Doyle, Kathy M. O¿Boyle and Paul V. Murphy, Synthetic Approaches to Cell Proliferation Inhibitors, Abstracts of Papers, 230th ACS National Meeting, Washington, DC, United States, Aug 28-1 2005 (2005). Poster Presentation.
Paul M. O'Neill, Sarah L. Rawe, Kristina Borstnik, Alison Miller, Stephen A. Ward, Patrick G. Bray, Jill Davies, Chang Ho Oh, Gary H. Posner; Enantiomeric 1,2,4-Trioxanes Display Equivalent In Vitro Antimalarial Activity Versus Plasmodium falciparum Malaria Parasite: Implications for Molecular Mechanism of Action of Artemisinins; Chem BioChem, 2005, 2048-2054.
Paul M. O'Neill, Sarah L. Rawe, Richard C. Storr, Stephen A. Ward and Gary H. Posner; Lewis acid catalysed rearrangements of unsaturated bicyclic [2.2.n] endoperoxides in the presence of vinyl silanes; access to novel Fenozan BO-7 analogues; Tetrahedron Lett.; 2005; 3029-3032.