Associate Professor Mark Smythe
Associate Professor

Mark Smythe

Email: 
Phone: 
+61 7 334 62977

Availability

Associate Professor Mark Smythe is:
Available for supervision
Media expert

Fields of research

Medicinal and biomolecular chemistry Organic chemistry

Qualifications

  • Bachelor of Science, James Cook University
  • Bachelor (Honours) of Science (Advanced), James Cook University
  • Doctor of Philosophy, University of Melbourne

Research interests

  • 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.

  • 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.

  • 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.

  • 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.

Search Professor Mark Smythe’s works on UQ eSpace

57 works between 1993 and 2024
All (57) Journal Article (45) Book Chapter (1) Conference Publication (11)

1 - 20 of 57 works

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

Acid-sensing ion channel 1a blockade reduces myocardial injury in rodent models of myocardial infarction

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

Hematopoietic prostaglandin D synthase inhibitor PK007 decreases muscle necrosis in DMD mdx model mice

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

PGD2/DP2 receptor activation promotes severe viral bronchiolitis by suppressing IFN-λ production

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.

Hepcidin Mimetic Ptg-300 for Treatment of Ineffective Erythropoiesis and Iron Overload

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

Clustering of disulfide-rich peptides provides scaffolds for hit discovery by phage display: application to interleukin-23

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

Discovery and characterization of a potent interleukin-6 binding peptide with neutralizing activity in vivo

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

Conformational searching using a population-based incremental learning algorithm

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

Sigma-class glutathione transferases

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

Defining scaffold geometries for interacting with proteins: Geometrical classification of secondary structure linking regions

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

Development and characterization of new inhibitors of the human and mouse hematopoietic prostaglandin D-2 synthases

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

Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D-2 synthase

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

Design, synthesis and evaluation of inhibitors targeting the SHP-1 catalytic domain

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

Library of biphenyl privileged substructures using a safety-catch linker approach

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

Cyclic tetrapeptides via the ring contraction strategy: Chemical techniques useful for their identification

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

A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries

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

A convenient method for synthesis of cyclic peptide libraries

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

A safety catch linker for Fmoc-based assembly of constrained cyclic peptides

2005

Book Chapter

A convenient method for the synthesis of cyclic peptide libraries

Bourne, Gregory T., Nielson, Jonathon L., Coughlan, Justin F., Darwen, Paul, Campitelli, Marc R., Horton, Douglas A., Rhumann, Andreas, Love, Stephen G., Tran, Tran T. and Smythe, Mark L. (2005). A convenient method for the synthesis of cyclic peptide libraries. Peptide synthesis and applications. (pp. 151-166) edited by John Howl. Clifton, NJ, USA: Humana Press.

A convenient method for the synthesis of cyclic peptide libraries

2005

Journal Article

Intramolecular disulphide bond arrangements in nonhomologous proteins

Hartig, Gerald R. S., Tran, Tran T. and Smythe, Mark L. (2005). Intramolecular disulphide bond arrangements in nonhomologous proteins. Protein Science, 14 (2), 474-482. doi: 10.1110/ps.04923305

Intramolecular disulphide bond arrangements in nonhomologous proteins

2005

Journal Article

A versatile synthetic approach to peptidyl privileged structures using a "safety-catch" linker

Horton, Douglas A., Severinsen, Rune, Kofod-Hansen, Mikael, Bourne, Gregorty T. and Smythe, Mark L. (2005). A versatile synthetic approach to peptidyl privileged structures using a "safety-catch" linker. Journal of Combinatorial Chemistry, 7 (3), 421-435. doi: 10.1021/cc049829q

A versatile synthetic approach to peptidyl privileged structures using a "safety-catch" linker

Current funding

  • 2022 - 2025
    Developing treatments for Duchenne Muscular Dystrophy
    Muscular Dystrophy Association
    Open grant

Past funding

  • 2020 - 2023
    Towards the treatment of Duchenne Muscular Dystrophy
    NHMRC Development Grant
    Open grant
  • 2019
    Chemical Purification Network
    UQ Major Equipment and Infrastructure
    Open grant
  • 2019
    In vivo imaging system for tracking inflammation, infection, cancer, pain and bioactive molecules
    UQ Major Equipment and Infrastructure
    Open grant
  • 2018
    Multichannel peptide synthesiser to accelerate UQ's biodiscovery pipeline and peptide drug development programs
    UQ Major Equipment and Infrastructure
    Open grant
  • 2017 - 2018
    Evaluation of the Safety of Lead Compounds for Allergic Asthma
    NHMRC Development Grant
    Open grant
  • 2016
    Integrative blood coagulation research core facility
    UQ Major Equipment and Infrastructure
    Open grant
  • 2016 - 2017
    The Development of Human Hematopoietic Prostaglandin D2 Synthase Inhibitors (HPGD2S) For Allergic Asthma
    National Foundation for Medical Research and Innovation
    Open grant
  • 2014
    Continuous-Flow Hydrogenation Reactor (H-Cube Pro)
    UQ Major Equipment and Infrastructure
    Open grant
  • 2014 - 2016
    Towards treatment of asthma
    NHMRC Development Grant
    Open grant
  • 2013 - 2014
    Extending frontiers of structural chemistry and biology through high resolution pulsed electron paramagnetic resonance (ARC LIEF Grant administered by the University of Melbourne)
    University of Melbourne
    Open grant
  • 2013
    Establishment of an Integrated Facility for Single Cell Analysis
    UQ Major Equipment and Infrastructure
    Open grant
  • 2012 - 2016
    Contract research program for Protagonist Pty Ltd
    UniQuest Pty Ltd
    Open grant
  • 2012
    Analytical flow cytometer for cell and developmental biology and drug discovery applications
    UQ Major Equipment and Infrastructure
    Open grant
  • 2012 - 2015
    Targeting of the Myb-p300 Interaction in Myeloid Leukaemogenesis
    NHMRC Project Grant
    Open grant
  • 2012 - 2014
    The development of human hematopoietic prostaglandin D2 synthase inhibitors in allergic asthma and related disorders
    NHMRC Development Grant
    Open grant
  • 2010
    Combinatorial chemistry (high throughput synthesizer and purification system)
    UQ Major Equipment and Infrastructure
    Open grant
  • 2010
    Resonant waveguide label-free plate sensor
    UQ Major Equipment and Infrastructure
    Open grant
  • 2007 - 2009
    Design and use of human hematopoietic prostaglandin D2 synthase inhibitors in allergic asthma and bone diseases
    NHMRC Project Grant
    Open grant
  • 2006 - 2008
    Common Recognition Elements In Protein Active Sites: Improving The Efficiencies Of Drug Discovery
    ARC Discovery Projects
    Open grant
  • 2006 - 2007
    Role, and potential for therapeutic targeting, of transcriptional co-regulators in transformation by the MYB oncogene
    Queensland Cancer Fund
    Open grant
  • 2005 - 2006
    ESEG_Australian Microbial Biodiscovery: Exploration of Bioactive Chemical Space
    UQ External Support Enabling Grant
    Open grant
  • 2002 - 2004
    Biocore 3000 for discovery and characterisation of novel pharmaceuticals
    Systemic Infrastucture Iniative
    Open grant
  • 2001 - 2003
    Strategies towards the solid phase synthesis of cyclic tera-and pentapeptide libraries.
    ARC Australian Research Council (Large grants)
    Open grant
  • 2001
    Strategies towards the solid phase synthesis of cyclic tetra and pentaptide libraries
    University of Queensland Small Grants Scheme
    Open grant
  • 2000 - 2002
    The development of small molecule growth hormone agonists
    ARC Collaborative Grant (SPIRT)
    Open grant
  • 2000 - 2002
    The discovery of side chain conformational motifs that are important in protein recognition.
    ARC Australian Research Council (Large grants)
    Open grant
  • 1998 - 2000
    The Development of Cytokine Mimetics
    NHMRC Project Grant
    Open grant
  • 1997 - 1999
    Approaches to the development of drugs for Alzheimer's disease
    NHMRC Project Grant
    Open grant
  • 1997
    Peptide cyclisation auxiliaries
    ARC Australian Research Council (Small grants)
    Open grant
  • 1997 - 1999
    Proteases involved in haemoglobin digestion as novel targets against schistosomiasis
    Queensland Institute of Medical Research
    Open grant
  • 1996 - 2000
    Constrained cyclic peptides
    Glaxo Wellcome Australia Limited
    Open grant
  • 1996
    Approaches to the development of drugs for Alzheimer's disease
    NHMRC Project - Special Initiative Grant
    Open grant
  • 1996
    Approaches to the development of drugs for Alzheimer's disease
    UQ External Support Enabling Grant
    Open grant
  • 1996 - 1998
    Developing artificial antibodies
    NHMRC Project Grant - HIV/AIDS (CARG)
    Open grant
  • 1995 - 1996
    The development of inhibitors of HIV which block the binding of virus to cell
    DIST - Department Industry, Science and Tourism
    Open grant

Availability

Associate Professor Mark Smythe is:
Available for supervision

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Supervision history

Current supervision

Completed supervision

  • 2012

    Doctor Philosophy

    Substrate-based Design of SHP-1 Inhibitors

    Principal Advisor

  • 2008

    Doctor Philosophy

    Drugs for undruggable targets and other impossibilities: The development of molecular scaffolds for more efficient drug design and development

    Principal Advisor

  • 2005

    Doctor Philosophy

    THE SYNTHESIS OF PRIVILEGED SUBSTRUCTURES

    Principal Advisor

  • 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

  • 2004

    Doctor Philosophy

    COMBINATORIAL METHODS AND APPLICATIONS IN DRUG DISCOVERY

    Associate Advisor

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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