
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
2024
Journal Article
Dual therapy with corticosteroid ablates the beneficial effect of DP2 antagonism in chronic experimental asthma
Ullah, Md Ashik, Rittchen, Sonja, Li, Jia, Curren, Bodie F., Namubiru, Patricia, Ahmed, Tufael, Howard, Daniel R., Rahman, Muhammed Mahfuzur, Sikder, Md Al Amin, Rashid, Ridwan B., Collinson, Natasha, Lor, Mary, Smythe, Mark L. and Phipps, Simon (2024). Dual therapy with corticosteroid ablates the beneficial effect of DP2 antagonism in chronic experimental asthma. Nature Communications, 15 (1) 10253, 1-13. doi: 10.1038/s41467-024-54670-8
2024
Journal Article
Prostaglandins in the inflamed central nervous system: potential therapeutic targets
Sheremeta, Chynna-Loren, Yarlagadda, Sai, Smythe, Mark L. and Noakes, Peter G. (2024). Prostaglandins in the inflamed central nervous system: potential therapeutic targets. Current Drug Targets, 25 (13), 885-908. doi: 10.2174/0113894501323980240815113851
2024
Journal Article
Acid-sensing ion channel 1a blockade reduces myocardial injury in rodent models of myocardial infarction
Redd, Meredith A, Yoshikawa, Yusuke, Khan, Nemat, Waqar, Maleeha, Saez, Natalie J, Outhwaite, Jennifer E, Russell, Jake S, Hanna, Amy D, Chiu, Han S, Er, Sing Yan, Butcher, Neville J, Mardon, Karine, Fraser, John F, Smythe, Mark L, Rash, Lachlan D, Thomas, Walter G, King, Glenn F, Reichelt, Melissa E and Palpant, Nathan J (2024). Acid-sensing ion channel 1a blockade reduces myocardial injury in rodent models of myocardial infarction. European Heart Journal, 45 (17), 1571-1574. doi: 10.1093/eurheartj/ehad793
2021
Journal Article
Hematopoietic prostaglandin D synthase inhibitor PK007 decreases muscle necrosis in DMD mdx model mice
Yarlagadda, Sai, Kulis, Christina, Noakes, Peter G. and Smythe, Mark L. (2021). Hematopoietic prostaglandin D synthase inhibitor PK007 decreases muscle necrosis in DMD mdx model mice. Life, 11 (9) 994, 994. doi: 10.3390/life11090994
2018
Journal Article
PGD2/DP2 receptor activation promotes severe viral bronchiolitis by suppressing IFN-λ production
Werder, Rhiannon B., Lynch, Jason P., Simpson, Jennifer C., Zhang, Vivian, Hodge, Nick H., Poh, Matthew, Forbes-Blom, Elizabeth, Kulis, Christina, Smythe, Mark L., Upham, John W., Spann, Kirsten, Everard, Mark L. and Phipps, Simon (2018). PGD2/DP2 receptor activation promotes severe viral bronchiolitis by suppressing IFN-λ production. Science Translational Medicine, 10 (440) eaao0052, eaao0052. doi: 10.1126/scitranslmed.aao0052
2017
Conference Publication
Hepcidin Mimetic Ptg-300 for Treatment of Ineffective Erythropoiesis and Iron Overload
Bourne, Gregory, Zhao, Li, Bhandari, Ashok, Frederick, Brian, McMahon, Jaimee, Tran, Vinh, Zhang, Jenny, Stephenson, Adam, Tovera, James, Bai, Lu, Annamalai, Thamil, Patel, Dinesh, Smythe, Mark and Liu, David (2017). Hepcidin Mimetic Ptg-300 for Treatment of Ineffective Erythropoiesis and Iron Overload. Seventh Congress of the International BioIron Society (IBIS)Biennial World Meeting (BioIron 2017), Los Angeles, CA, United States, 7 - 11 May 2017. Hoboken, NJ United States: Wiley.
2016
Journal Article
Clustering of disulfide-rich peptides provides scaffolds for hit discovery by phage display: application to interleukin-23
Barkan, David T., Cheng, Xiao-Li, Celino, Herodion, Tran, Tran T., Bhandari, Ashok, Craik, Charles S., Sali, Andrej and Smythe, Mark L. (2016). Clustering of disulfide-rich peptides provides scaffolds for hit discovery by phage display: application to interleukin-23. BMC Bioinformatics, 17 (481) 481, 481. doi: 10.1186/s12859-016-1350-9
2015
Journal Article
Discovery and characterization of a potent interleukin-6 binding peptide with neutralizing activity in vivo
Ranganath, Sheila, Bhandari, Ashok, Avitahl-Curtis, Nicole, McMahon, Jaimee, Wachtel, Derek, Zhang, Jenny, Leitheiser, Christopher, Bernier, Sylvie G., Liu, Guang, Tran, Tran T., Celino, Herodion, Tobin, Jenny, Jung, Joon, Zhao, Hong, Glen, Katie E., Graul, Chris, Griffin, Aliesha, Schairer, Wayne C., Higgins, Carolyn, Reza, Tammi L., Mowe, Eva, Rivers, Sam, Scott, Sonya, Monreal, Alex, Shea, Courtney, Bourne, Greg, Coons, Casey, Smith, Adaline, Tang, Kim ... Carlson, Kenneth E. (2015). Discovery and characterization of a potent interleukin-6 binding peptide with neutralizing activity in vivo. PLoS One, 10 (11) e0141330, 1-19. doi: 10.1371/journal.pone.0141330
2011
Journal Article
Conformational searching using a population-based incremental learning algorithm
Long, Stephen M., Tran, Tran T., Adams, Peter, Darwen, Paul and Smythe, M. L. (2011). Conformational searching using a population-based incremental learning algorithm. Journal of Computational Chemistry, 32 (8), 1541-1549. doi: 10.1002/jcc.21732
2011
Journal Article
Sigma-class glutathione transferases
Flanagan, Jack U. and Smythe, Mark L. (2011). Sigma-class glutathione transferases. Drug Metabolism Reviews, 43 (2), 194-214. doi: 10.3109/03602532.2011.560157
2010
Journal Article
Defining scaffold geometries for interacting with proteins: Geometrical classification of secondary structure linking regions
Tran, Tran T., Kulis, Christina, Long, Steven M., Bryant, Darryn, Adams, Peter and Smythe, Mark L. (2010). Defining scaffold geometries for interacting with proteins: Geometrical classification of secondary structure linking regions. Journal of Computer-Aided Molecular Design, 24 (11), 917-934. doi: 10.1007/s10822-010-9384-y
2010
Journal Article
Development and characterization of new inhibitors of the human and mouse hematopoietic prostaglandin D-2 synthases
Christ, Angelika N., Labzin, Larisa, Bourne, Gregory T., Fukunishi, Hirotada, Weber, Jane E., Sweet, Matthew J., Smythe, Mark L. and Flanagan, Jack U. (2010). Development and characterization of new inhibitors of the human and mouse hematopoietic prostaglandin D-2 synthases. Journal of Medicinal Chemistry, 53 (15), 5536-5548. doi: 10.1021/jm100194a
2010
Journal Article
Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D-2 synthase
Weber, Jane E., Oakley, Aaron J., Christ, Angelika N., Hayes, John D., Hall, Rhonda, Hume, David A., Board, Philip G., Smythe, Mark L. and Flanagan, Jack U. (2010). Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D-2 synthase. European Journal of Medicinal Chemistry, 45 (2), 447-454. doi: 10.1016/j.ejmech.2009.10.025
2010
Conference Publication
Design, synthesis and evaluation of inhibitors targeting the SHP-1 catalytic domain
Kulis, C., Bourne, G., Kellie, S. and Smythe, M. (2010). Design, synthesis and evaluation of inhibitors targeting the SHP-1 catalytic domain. EPS 2010: The 31st European Peptide Symposium, Copenhagen, Denmark, 5-9 September 2010. West Sussex, United Kingdom: John Wiley & Sons. doi: 10.1002/psc.1303
2008
Journal Article
Library of biphenyl privileged substructures using a safety-catch linker approach
Severinsen, Rune, Bourne, Gregory T., Tran, Tran T., Ankersen, Michael, Begtrup, Mikael and Smythe, Mark L. (2008). Library of biphenyl privileged substructures using a safety-catch linker approach. Journal of Combinatorial Chemistry, 10 (4), 557-566. doi: 10.1021/cc800006g
2008
Journal Article
Cyclic tetrapeptides via the ring contraction strategy: Chemical techniques useful for their identification
Horton, D. A., Bourne, 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 (8), 1386-1395. doi: 10.1039/b800464a
2006
Journal Article
A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries
Darwen, PJ, Tran, TT, Bourne, GT, Nielson, JL and Smythe, ML (2006). A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries. Combinatorial Chemistry & High Throughput Screening, 9 (7), 559-563. doi: 10.2174/138620706777935333
2005
Journal Article
A convenient method for synthesis of cyclic peptide libraries
Bourne, Gregory T, Nielson, Jonathon L, Coughlan, Justin F, Darwen, Paul, Campitelli, Marc R, Horton, Douglas A, Rhümann, Andreas, Love, Stephen G, Tran, Tran T and Smythe, Mark L (2005). A convenient method for synthesis of cyclic peptide libraries. Methods in molecular biology (Clifton, N.J.), 298, 151-165. doi: 10.1385/1-59259-877-3:151
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
2005
Journal Article
A safety catch linker for Fmoc-based assembly of constrained cyclic peptides
Ravn, J, Bourne, GT and Smythe, ML (2005). A safety catch linker for Fmoc-based assembly of constrained cyclic peptides. Journal of Peptide Science, 11 (9), 572-578. doi: 10.1002/psc.651
Funding
Current funding
Past funding
Supervision
Availability
- Associate Professor Mark Smythe is:
- Available for supervision
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Supervision history
Current supervision
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Doctor Philosophy
Assessing the therapeutic effects of our novel compound `PK007¿ in DMD model mice by inhibiting pro-inflammatory prostaglandin D2 synthesis.
Principal Advisor
Other advisors: Associate Professor Peter Noakes
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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
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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