2010 Annual Report - Institute for Molecular Bioscience - University ...

61 imb researchers: chemistry and structural biology
MARK SMYTHE
COMBINATORIAL CHEMISTRY AND
MOLECULAR DESIGN
• Developing new computational
algorithms and strategies for sampling
biologically-relevant chemistries
• Developing a synthetic process for the
combinatorial synthesis of biologicallyrelevant
compounds
• Developing in vitro and cell-based
assays for screening arrays of
compounds
OUR RESEARCH FOCUSES ON
advancing drug design and synthetic
organic and peptide chemistry to discover
novel biologically-active molecules. We
apply these new drug design and discovery
methodologies to discover drugs to treat
unmet medical needs or provide better
therapeutic solutions to existing marketed
drugs.
Using a combination of mathematics,
software development, drug design,
combinatorial chemistry and phage display,
we are developing new approaches to
identify biologically-active molecules. Thus,
projects are multidisciplinary and focused
on achieving medical outcomes.
We have recently developed several
small molecule anti-TNF compounds for
treatment of inflammatory diseases and
specific small molecule modulators of
prostaglandin D 2 synthase for treatment of
asthma. In addition we have designed and
synthesised a new spin label to accurately
determine distances in biological systems.
RESEARCH PROJECTS
• Modulating haematopoietic
prostaglandin D 2 synthase for allergic
disease
• Studying antagonists of Myb for
treatment of leukaemia
• Designing SHP-1 inhibitors to boost
haematopoiesis
• Developing antipathogenic compounds
to treat microbial infections
• Developing structure-based phage
display
KEY PUBLICATIONS
Horton, D.A., Horton, G.T., Coughlan, J.,
Kaiser, S.M., Jacobs, C.M., Jones, A.,
Ruhmann, A., Turner, J.Y., and Smythe,
M.L. (2008). Cyclic tetrapeptides via
the ring contraction strategy: chemical
techniques useful for their identification.
Organic & Biomolecular Chemistry 6:
1386-1395.
Severinsen, R., Bourne, G.T., Tran, T.T.,
Ankersen, M., Begtrup, M., and Smythe,
M.L. (2008). Library of Biphenyl Privleged
Substructures using a Safety-Catch
Linker Approach. Journal of Combinatorial
Chemistry 10: 557-566.
Horton, D.A., Severinsen, R., Kofod-
Hansen, M., Bourne, G.T., and Smythe,
M.L. (2005). A versatile synthetic
approach to peptidyl privileged structures
using a safety catch linker. Journal of
Combinatorial Chemistry 7: 421-435.
Horton, D.A., Bourne, G.T., and Smythe,
M.L. (2003). The Combinatorial Synthesis
of Bicyclic Privileged Structures or
Privileged Substructures. Chemical
Reviews 103: 893-930.
Meutermans, W.D.F., Bourne, G.T.,
Golding, S.W., Horton, D.A., Campitelli,
M.R., Craik, D., Scanlon, M., and Smythe,
M.L. (2003). Difficult Macrocyclisations:
New Strategies for Synthesising Highly
Strained Cyclic Tetrapeptides. Organic
Letters 5: 2711-2714.
LAB MEMBERS
Senior Research Officers: Dr Craig
Murphy, Dr Greg Bourne, Dr Nicole
Lawrence
Research Officers: Dr Katie Glenn, Dr
Jenny Zhang, Dr Rosemary Harrison
Research Assistants: Jill Turner, Jaimee
Duncan, Angelika Christ, Aleisha Griffin,
Phillip Walsh
PhD Student: Christina Kulis