Associate Professor Mark Smythe
Associate Professor

Mark Smythe

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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

63 works between 1993 and 2024
All (63) Journal Article (48) Book Chapter (1) Conference Publication (14)

41 - 60 of 63 works

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.

Incorporation of a cis-amide bond isostere in the synthesis of cyclic tetrapeptides

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.

The use of a novel safety catch linker for BOC-based assembly of cyclic peptide libraries

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.

Privilege structures: New strategies for the synthesis of cyclic tetrapepties

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+

An Activated O N Acyl Transfer Auxiliary: Efficient Amide-Backbone Substitution of Hindered "Difficult" Peptides

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.

An evaluation of a novel safety catch linker for the development of cyclic peptide libraries

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

Toward larger chemical libraries: Encoding with fluorescent colloids in combinatorial chemistry

2000

Conference Publication

Synthesis of small cyclic peptides: An auxiliary approach to address the difficult cyclization problem

Meutermans, W., Golding, S., Bourne, G. T., Miranda, L. P., Dooley, M., Alewood, P. F. and Smythe, M. L. (2000). Synthesis of small cyclic peptides: An auxiliary approach to address the difficult cyclization problem. 16th American Peptide Symposium, Minneapolis, MN United States, 26 June - 1 July 1999. Dordrecht, Netherlands: Kluwer. doi: 10.1007/0-306-46881-6_75

Synthesis of small cyclic peptides: An auxiliary approach to address the difficult cyclization problem

2000

Journal Article

Exploring privileged structures: The combinatorial synthesis of cyclic peptides

Horton, DA, Bourne, GT and Smythe, ML (2000). Exploring privileged structures: The combinatorial synthesis of cyclic peptides. Molecular Diversity, 5 (4), 289-304. doi: 10.1023/A:1021365402751

Exploring privileged structures: The combinatorial synthesis of cyclic peptides

2000

Journal Article

Synthesis of difficult cyclic peptides by inclusion of a novel photolabile auxiliary in a ring contraction strategy

Scolastico, C., Manzoni, L., Meutermans, W. D.F., Golding, S. W., Bourne, G. T., Miranda, L. P., Dooley, M. J., Alewood, P. F. and Smythe, M. L. (2000). Synthesis of difficult cyclic peptides by inclusion of a novel photolabile auxiliary in a ring contraction strategy. Chemtracts, 13 (7), 443-446.

Synthesis of difficult cyclic peptides by inclusion of a novel photolabile auxiliary in a ring contraction strategy

2000

Conference Publication

The side-chain classification of loops from high resolution protein crystal structures

Tran, T. T., Bourne, G. T., Golding, S., Meutermans, W. and Smythe, M. L. (2000). The side-chain classification of loops from high resolution protein crystal structures. 16th American Peptide symposium, Minneapolis, MN United States, 26 June - 1 July 1999. Dordrecht, Netherlands: Kluwer. doi: 10.1007/0-306-46881-6_130

The side-chain classification of loops from high resolution protein crystal structures

1999

Journal Article

The development of solid phase protocols for a backbone amide linker and its application to the Boc-based assembly of linear peptides

Bourne, G. T., Meutermans, W. D. F. and Smythe, M. L. (1999). The development of solid phase protocols for a backbone amide linker and its application to the Boc-based assembly of linear peptides. Tetrahedron Letters, 40 (40), 7271-7274. doi: 10.1016/S0040-4039(99)01473-2

The development of solid phase protocols for a backbone amide linker and its application to the Boc-based assembly of linear peptides

1999

Journal Article

A Backbone Linker for BOC-Based Peptide Synthesis and On-Resin Cyclization: Synthesis of Stylostatin 1

Bourne, GT, Meutermans, WDF, Alewood, PF, McGeary, RP, Watson, AA and Smythe, ML (1999). A Backbone Linker for BOC-Based Peptide Synthesis and On-Resin Cyclization: Synthesis of Stylostatin 1. Journal of Organic Chemistry, 64 (9), 3095-3101. doi: 10.1021/jo9818780

A Backbone Linker for BOC-Based Peptide Synthesis and On-Resin Cyclization: Synthesis of Stylostatin 1

1997

Journal Article

Proteolytic degradation of host hemoglobin by schistosomes

Brindley, Paul J., Kalinna, Bernd H., Dalton, John P., Day, Sharon R., Wong, Joanna Y. M., Smythe, Mark L. and McManus, Donald P. (1997). Proteolytic degradation of host hemoglobin by schistosomes. Molecular and Biochemical Parasitology, 89 (1), 1-9. doi: 10.1016/S0166-6851(97)00098-4

Proteolytic degradation of host hemoglobin by schistosomes

1997

Journal Article

Synthesis of alpha-aspartyl-containing cyclic peptides

Meutermans, WDF, Alewood, PF, Bourne, GT, Hawkins, B and Smythe, ML (1997). Synthesis of alpha-aspartyl-containing cyclic peptides. Letters In Peptide Science, 4 (2), 79-84. doi: 10.1023/A:1008878017315

Synthesis of alpha-aspartyl-containing cyclic peptides

1997

Journal Article

Synthesis of α-aspartyl-containing cyclic peptides

Meutermans W.D.F., Alewood P.F., Bourne G.T., Hawkins B. and Smythe M.L. (1997). Synthesis of α-aspartyl-containing cyclic peptides. Letters in Peptide Science, 4 (2), 79-84. doi: 10.1007/BF02443518

Synthesis of α-aspartyl-containing cyclic peptides

1996

Journal Article

VALIDATE: A new method for the receptor-based prediction of binding affinities of novel ligands

Head, RD, Smythe, ML, Oprea, TI, Waller, CL, Green, SM and Marshall, GR (1996). VALIDATE: A new method for the receptor-based prediction of binding affinities of novel ligands. Journal of the American Chemical Society, 118 (16), 3959-3969. doi: 10.1021/ja9539002

VALIDATE: A new method for the receptor-based prediction of binding affinities of novel ligands

1996

Journal Article

Electrochemical cyclization of dipeptides to form novel bicyclic, reverse-turn peptidomimetics. 2. Synthesis and conformational analysis of 6,5-bicyclic systems

Slomezynska, Urszula, Chalmers, David K., Cornille, Fabrice, Smythe, Mark L., Beusen, Denise D., Moeller, Kevin D. and Marshall, Garland R. (1996). Electrochemical cyclization of dipeptides to form novel bicyclic, reverse-turn peptidomimetics. 2. Synthesis and conformational analysis of 6,5-bicyclic systems. Journal of Organic Chemistry, 61 (4), 1198-1204. doi: 10.1021/jo950898o

Electrochemical cyclization of dipeptides to form novel bicyclic, reverse-turn peptidomimetics. 2. Synthesis and conformational analysis of 6,5-bicyclic systems

1995

Journal Article

Electrochemical Cyclization of Dipeptides toward Novel Bicyclic, Reverse-Turn Peptidomimetics. 1. Synthesis and Conformational Analysis of 7,5-Bicyclic Systems

Cornille F., Slomczynska U., Smythe M.L., Marshall G.R., Beusen D.D., Marshall G.R., Moeller K.D., Slomczynska U., Slomczynska U., Cornille F. and Smythe M.L. (1995). Electrochemical Cyclization of Dipeptides toward Novel Bicyclic, Reverse-Turn Peptidomimetics. 1. Synthesis and Conformational Analysis of 7,5-Bicyclic Systems. Journal of Organic Chemistry, 117 (3), 909-917. doi: 10.1021/ja00108a007

Electrochemical Cyclization of Dipeptides toward Novel Bicyclic, Reverse-Turn Peptidomimetics. 1. Synthesis and Conformational Analysis of 7,5-Bicyclic Systems

1995

Journal Article

α-Helical versus 310-Helical Conformation of Alanine-Based Peptides in Aqueous Solution: An Electron Spin Resonance Investigation

Smythe M.L., Nakaie C.R. and Marshall G.R. (1995). α-Helical versus 310-Helical Conformation of Alanine-Based Peptides in Aqueous Solution: An Electron Spin Resonance Investigation. Journal of the American Chemical Society, 117 (42), 10555-10562. doi: 10.1021/ja00147a018

α-Helical versus 310-Helical Conformation of Alanine-Based Peptides in Aqueous Solution: An Electron Spin Resonance Investigation

1995

Journal Article

The Molten Helix: Effects of Solvation on the α- to 310-Helical Transition

Smythe M.L., Huston S.E. and Marshall G.R. (1995). The Molten Helix: Effects of Solvation on the α- to 310-Helical Transition. Journal of the American Chemical Society, 117 (20), 5445-5452. doi: 10.1021/ja00125a003

The Molten Helix: Effects of Solvation on the α- to 310-Helical Transition

Current funding

  • 2025 - 2027
    Targeting Prostaglandin D2 Pathway for Enhanced Therapy in Atopic Dermatitis
    NHMRC Development Grant
    Open grant
  • 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

  • Doctor Philosophy

    Blocking the sensing function of activated glia during neuroinflammation

    Principal Advisor

    Other advisors: Associate Professor Peter Noakes

  • Doctor Philosophy

    Blocking the sensing function of activated glia during neuroinflammation

    Principal Advisor

    Other advisors: Associate Professor Peter Noakes

  • Doctor Philosophy

    Towards the Treatment of Duchenne Muscular Dystrophy

    Principal Advisor

    Other advisors: Associate Professor Peter Noakes

  • 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

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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