Overview
Availability
- Associate Professor Mark Smythe is:
- Available for supervision
- Media expert
Fields of research
Qualifications
- Bachelor of Science, James Cook University
- Bachelor (Honours) of Science (Advanced), James Cook University
- Doctor of Philosophy, University of Melbourne
Research interests
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Combinatorial Chemistry and Molecular Design
The approach is to combine protein structural information with combinatorial chemistry, resulting in the design and synthesis of molecules that mimic protein structure, ultimately leading to the discovery of compounds that mimic protein function. We are actively pursuing small molecules for cytokine and G-protein coupled receptors.
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Protein-protein interactions
Many biological processes are carried out, or regulated, through protein-protein interactions. Despite their physiological significance, they remain one of the most difficult molecular recognition events to inhibit or mimic. We have developed molecular design processes that successfully identify small molecular candidates which modulate the function of protein-protein interactions. We currently have several lead molecules against numerous protein-protein interaction targets.
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Molecular design
We have developed an integrated design platform for library design and structure-based design of molecules that modulate protein-protein interactions. This approach includes a set of unique biological descriptors for library design, a purpose-built virtual screening of virtual library platform and databases comprising large virtual libraries of compounds. Using these methodologies we design and synthesise arrays of molecules that sample biologically relevant diversity space for primary screening, as well as arrays of molecules specifically targetted for a therapeutic protein of interest.
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Combinatorial chemistry
Current strategies in library design involve the calculation of hundreds of potential descriptors that define various chemical characteristics, and selecting a diverse set of compounds in this descriptor space. With hundreds of available descriptors it is difficult to know which descriptors, if any, are important or essential for describing biological activity. Consequently such procedures result in the optimisation of libraries in chemical descriptor space, which has little impact on biologically relevant regions of that space. To overcome this we have developed a series of biologically-relevant descriptors that are used in library design. As a consequence, we aim to identify the biologically-relevant structural regions of chemical diversity and design and synthesise arrays of molecules that match this diversity space. We have developed new linkers and auxiliaries to aid combinatorial synthesis and a molecular design platform to achieve these objectives. We have synthesised various constrained cyclic peptide libraries (molecular toolkit libraries) and libraries of macrocycles and heterocycles. We have a particular focus on the discovery and exploitation of privileged structures.
Works
Search Professor Mark Smythe’s works on UQ eSpace
2005
Journal Article
Topological side-chain classification of beta-turns: Ideal motifs for peptidomimetic development
Tran, TT, McKie, J, Meutermans, WDF, Bourne, GT, Andrews, PR and Smythe, ML (2005). Topological side-chain classification of beta-turns: Ideal motifs for peptidomimetic development. Journal of Computer-aided Molecular Design, 19 (8), 551-566. doi: 10.1007/s10822-005-9006-2
2004
Journal Article
Virtual drug discovery using graph
Adams, P., Bryant, D. E., Long, S., Smythe, M. L. and Tran, T. T. (2004). Virtual drug discovery using graph. Bulletin of the Institute of Combinatorics and its Applications, 40, 100-106.
2004
Journal Article
Increased site 1 affinity improves biopotency of porcine growth hormone - Evidence against diffusion dependent receptor dimerization
Wan, Y., McDevitt, A., Shen, B. J., Smythe, M. L. and Waters, M. J. (2004). Increased site 1 affinity improves biopotency of porcine growth hormone - Evidence against diffusion dependent receptor dimerization. Journal of Biological Chemistry, 279 (43), 44775-44784. doi: 10.1074/jbc.M406092200
2004
Conference Publication
From Omega-Conotoxins to Macrocycle Mimetics
Schroeder, CI, Nielsen, KJ, Adams, DA, Loughnan, M, Thomas, L, Bourne, GT, Smythe, ML, Alewood, PF, Craik, DJ and Lewis, RJ (2004). From Omega-Conotoxins to Macrocycle Mimetics. CHICHESTER: JOHN WILEY & SONS LTD.
2004
Journal Article
Development of small molecules that mimic the binding of w-conotoxins at the N-type voltage-gated calcium channel
Schroeder, I.C., Smythe, M. L. and Lewis, R. J. (2004). Development of small molecules that mimic the binding of w-conotoxins at the N-type voltage-gated calcium channel. Molecular Diversity, 8 (2), 127-134. doi: 10.1023/B:MODI.0000025656.79632.86
2003
Journal Article
Difficult macrocyclizations: New strategies for synthesizing highly strained cyclic tetrapeptides
Meutermans, W., Bourne, G. T., Golding, S., Horton, D., Campitelli, M. R., Craik, D. J., Scanlon, M. J. and Smythe, M. L. (2003). Difficult macrocyclizations: New strategies for synthesizing highly strained cyclic tetrapeptides. Organic Letters, 5 (15), 2711-2714. doi: 10.1021/ol034907o
2003
Journal Article
The combinatorial synthesis of bicyclic privileged structures or privileged substructures
Horton, DA, Bourne, GT and Smythe, ML (2003). The combinatorial synthesis of bicyclic privileged structures or privileged substructures. Chemical Reviews, 103 (3), 893-930. doi: 10.1021/cr020033s
2002
Journal Article
Exploring privileged structures: the combinatorial synthesis of cyclic peptides
Horton, D. A., Bourne, G. T. and Smythe, M. L. (2002). Exploring privileged structures: the combinatorial synthesis of cyclic peptides. Journal of Computer-aided Molecular Design, 16 (5-6), 415-431. doi: 10.1023/A:1020863921840
2002
Journal Article
A subset-oriented algorithm for minimizing the number of steps required for synthesis of cyclic-peptide libraries
Tran, T. T., Bryant, D. E. and Smythe, M. L. (2002). A subset-oriented algorithm for minimizing the number of steps required for synthesis of cyclic-peptide libraries. Computers and Chemistry, 26 (2), 113-117. doi: 10.1016/S0097-8485(01)00087-0
2002
Conference Publication
Clues to interaction between CSF-1 and CSF-1R from specificity and structure
Hamwood, T., Kobe, B., Smythe, M. L. and Hume, D. A. (2002). Clues to interaction between CSF-1 and CSF-1R from specificity and structure. Australian Society of Immunologists Meeting, Brisbane, 1-5 December, 2002.
2001
Conference Publication
Privilege structures: New strategies for the synthesis of cyclic tetrapepties
Meutermans, W., Golding, S., Campitelli, M.R., Horton, D., Bourne, G. T. and Smythe, M. L. (2001). Privilege structures: New strategies for the synthesis of cyclic tetrapepties. 17th AFS, San Diego, 9-15th June, 2001. USA: American Peptide Society.
2001
Journal Article
The development and application of a novel safety-catch linker for BOC-based assembly of libraries of cyclic peptides
Bourne, Gregory T., Golding, Simon W., McGeary, Ross P., Meutermans, Wim D. F., Jones, Alun, Marshall, Garland R., Alewood, Paul F. and Smythe, Mark L. (2001). The development and application of a novel safety-catch linker for BOC-based assembly of libraries of cyclic peptides. Journal of Organic Chemistry, 66 (23), 7706-7713. doi: 10.1021/jo010580y
2001
Journal Article
Synthesis of a cyclic peptide library based on the somatostatin sequence using the backbone amide linker approach
Bourne, G.T., Golding, S., Meutermans, W. and Smythe, M.L. (2001). Synthesis of a cyclic peptide library based on the somatostatin sequence using the backbone amide linker approach. Letters in Peptide Science, 7 (6), 311-316. doi: 10.1023/A:1013057832044
2001
Journal Article
Proteolysis of human hemoglobin by schistosome cathepsin D
Brindley, P. J., Kalinna, B. H., Wong, J. Y. M., Bogitsh, B. J., King, L. T., Smyth, D. J., Verity, C. K., Abbenante, G., Brinkworth, R. I., Fairlie, D. P., Smythe, M. L., Milburn, P. J., Bielefeldt-Ohmann, H., Zheng, Y. and McManus, D. P. (2001). Proteolysis of human hemoglobin by schistosome cathepsin D. Molecular And Biochemical Parasitology, 112 (1), 103-112. doi: 10.1016/S0166-6851(00)00351-0
2001
Conference Publication
Colloidal barcoding in combinatorial chemistry
Battersby, B. J., Bryant, D. E., Meutermans, W. and Smythe, M. L. (2001). Colloidal barcoding in combinatorial chemistry. Innovation & Perspectives in Solid Phase Synthesis & Combinatl, York, England, 31 Aug - 4 Sept, 1999. UK: Mayflower.
2001
Conference Publication
Incorporation of a cis-amide bond isostere in the synthesis of cyclic tetrapeptides
Bourne, G. T., Cassidy, P.J., Meutermans, W., Campitelli, M.R. and Smythe, M.L. (2001). Incorporation of a cis-amide bond isostere in the synthesis of cyclic tetrapeptides. Peptides: The wave of the future, San Diego, 9-14/6/01. USA: American Peptide Society.
2001
Conference Publication
The use of a novel safety catch linker for BOC-based assembly of cyclic peptide libraries
Golding, S.W., Bourne, G.T., Meutermans, W.D.F., Jones, A. and Smythe, M.L. (2001). The use of a novel safety catch linker for BOC-based assembly of cyclic peptide libraries. 17th Australian Peptide Conference, San Diego, Calafornia, 9-14 June, 2001. USA: American Peptide Society.
2000
Journal Article
An Activated O N Acyl Transfer Auxiliary: Efficient Amide-Backbone Substitution of Hindered "Difficult" Peptides
Miranda, L. P., Meutermans, W. D. F., Smythe, M. L. and Alewood, P.F. (2000). An Activated O N Acyl Transfer Auxiliary: Efficient Amide-Backbone Substitution of Hindered "Difficult" Peptides. Journal of Organic Chemistry, 65 (18), 5460-5468. doi: 10.1021/jo991340+
2000
Conference Publication
An evaluation of a novel safety catch linker for the development of cyclic peptide libraries
Bourne, G. T., McGeary, R. P., Golding, S., Meutermans, W., Alewood, P. F. and Smythe, M. L. (2000). An evaluation of a novel safety catch linker for the development of cyclic peptide libraries. 16th American Peptide Symposium, Minneapolis, MN United States, 26 June - 1 July 1999.
2000
Journal Article
Toward larger chemical libraries: Encoding with fluorescent colloids in combinatorial chemistry
Battersby, Bronwyn J., Bryant, Darryn, Meutermans, Wim, Matthews, Daniel, Smythe, Mark L. and Trau, Matt (2000). Toward larger chemical libraries: Encoding with fluorescent colloids in combinatorial chemistry. Journal of the American Chemical Society, 122 (9), 2138-2139. doi: 10.1021/ja993634i
Funding
Current funding
Past funding
Supervision
Availability
- Associate Professor Mark Smythe is:
- Available for supervision
Before you email them, read our advice on how to contact a supervisor.
Supervision history
Current supervision
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Doctor Philosophy
Blocking the sensing function of activated glia during neuroinflammation
Principal Advisor
Other advisors: Associate Professor Peter Noakes
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Doctor Philosophy
Towards the Treatment of Duchenne Muscular Dystrophy
Principal Advisor
Other advisors: Associate Professor Peter Noakes
Completed supervision
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2008
Doctor Philosophy
Drugs for undruggable targets and other impossibilities: The development of molecular scaffolds for more efficient drug design and development
Principal Advisor
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2005
Doctor Philosophy
THE SYNTHESIS OF PRIVILEGED SUBSTRUCTURES
Principal Advisor
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2007
Doctor Philosophy
THE STRUCTURAL BASIS FOR INTERACTION BETWEEN COLONY- STIMULATING FACTOR-1 AND ITS RECEPTOR, CSF-1R
Associate Advisor
Other advisors: Professor David Hume, Professor Bostjan Kobe, Dr Ian Ross
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2004
Doctor Philosophy
COMBINATORIAL METHODS AND APPLICATIONS IN DRUG DISCOVERY
Associate Advisor
Media
Enquiries
Contact Associate Professor Mark Smythe directly for media enquiries about:
- asthma
- Chemistry - combinatorial
- Chemistry - computational
- Computational chemistry
- Drug design
- drug development
- drug discovery
- inflammatory bowel disease
- leukaemia
- Molecular modelling
- peptides
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