Dr Markus Muttenthaler is a medicinal chemist working at the interface of chemistry and biology with a strong passion for translational research. His research focus is on neuropeptides and the exploration of nature's diversity (i.e. venom peptides) to develop molecular tools, diagnostics and therapeutics. His background in drug discovery, design and development, as well as his interdisciplinary training in the fields of chemistry, molecular biology and pharmacology assist him in the characterisation of these highly potent and selective compounds and allow him to study their interactions with human physiology for medical innovations neuropathic pain, cancer, autism, gastrointestinal disorders and neurodegenerative diseases.
Peptides are key mediators in many biological functions and understanding of their interaction with target proteins is fundamental to unravel the underlying mechanism of diseases. Over the years, an increasing number of bioactive peptides from animals, plants, and bacteria have been characterised, with the overwhelming realisation that these molecules often show better therapeutic performance than their human counterparts, particularly in terms of in vivo stability. The main research efforts situated in this field of Chemical Biology focus on the exploration and translation of these vast and untapped natural libraries towards the development of useful research tools and therapeutics. Solid-phase peptide synthesis, the main tool to access these compounds, is a powerful technology for the assembly and chemical modification of these highly chiral and structurally complex peptides. This complexity is also responsible for their remarkable selectivity and potency as well as for their low side effect profile observed in the clinic.
Journal Article: Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity
Liutkevičiūtė, Zita, Gil-Mansilla, Esther, Eder, Thomas, Casillas-Pérez, Barbara, Di Giglio, Maria Giulia, Muratspahić, Edin, Grebien, Florian, Rattei, Thomas, Muttenthaler, Markus, Cremer, Sylvia and Gruber, Christian W. (2018) Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity. The FASEB Journal, fj201800443. doi:10.1096/fj.201800443
Journal Article: Advancing the frontiers of chemical protein synthesis - the 7CPS meeting, Haifa, Israel
Conibear, Anne C. and Muttenthaler, Markus (2018) Advancing the frontiers of chemical protein synthesis - the 7CPS meeting, Haifa, Israel. Cell Chemical Biology, 25 3: 247-254. doi:10.1016/j.chembiol.2018.03.001
Journal Article: Contractility measurements of human uterine smooth muscle to aid drug development
Arrowsmith, Sarah, Keov, Peter, Muttenthaler, Markus and Gruber, Christian W. (2018) Contractility measurements of human uterine smooth muscle to aid drug development. Journal of Visualized Experiments, 2018 131: . doi:10.3791/56639
Aquatic chemo-modulators - a novel source for potent molecular probes
(2019–2021) ARC Discovery Projects
(2019) UQ Major Equipment and Infrastructure
In vivo imaging system for tracking inflammation, infection, cancer, pain and bioactive molecules
(2019) UQ Major Equipment and Infrastructure
Development of human trefoil factor 3 probes via structure and activity relationship study
Doctor Philosophy
Development of oxytocin receptor-specific tracers for breast tumour detection
Doctor Philosophy
Exploring the oxytocin receptor as a novel target for breast tumour inhibition
Doctor Philosophy
Oxytocin and Vasopressin Research
Please contact Dr Muttenthaler directly for further details
Venom peptide drug discovery
Please contact Dr Muttenthaler directly for further details.
Breast Cancer
Please contact Dr Muttenthaler directly for further details.
Selenocystine peptides - synthesis, folding and applications
Muttenthaler, M. and Alewood, P. F. (2009). Selenocystine peptides - synthesis, folding and applications. In Johannes Buchner (Ed.), Oxidative folding of peptides and proteins (pp. 396-418) Cambridge , U.K.: Royal Society of Chemistry.
Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity
Liutkevičiūtė, Zita, Gil-Mansilla, Esther, Eder, Thomas, Casillas-Pérez, Barbara, Di Giglio, Maria Giulia, Muratspahić, Edin, Grebien, Florian, Rattei, Thomas, Muttenthaler, Markus, Cremer, Sylvia and Gruber, Christian W. (2018) Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity. The FASEB Journal, fj201800443. doi:10.1096/fj.201800443
Advancing the frontiers of chemical protein synthesis - the 7CPS meeting, Haifa, Israel
Conibear, Anne C. and Muttenthaler, Markus (2018) Advancing the frontiers of chemical protein synthesis - the 7CPS meeting, Haifa, Israel. Cell Chemical Biology, 25 3: 247-254. doi:10.1016/j.chembiol.2018.03.001
Contractility measurements of human uterine smooth muscle to aid drug development
Arrowsmith, Sarah, Keov, Peter, Muttenthaler, Markus and Gruber, Christian W. (2018) Contractility measurements of human uterine smooth muscle to aid drug development. Journal of Visualized Experiments, 2018 131: . doi:10.3791/56639
Muttenthaler, Markus, Andersson, Asa, Vetter, Irina, Menon, Rohit, Busnelli, Marta, Ragnarsson, Lotten, Bergmayr, Christian, Arrowsmith, Sarah, Deuis, Jennifer R., Chiu, Han Sheng, Palpant, Nathan J., O'Brien, Margaret, Smith, Terry J., Wray, Susan, Neumann, Inga D., Gruber, Christian W., Lewis, Richard J. and Alewood, Paul F. (2017) Subtle modifications to oxytocin produce ligands that retain potency and improved selectivity across species. Science Signaling, 10 508: 1-13. doi:10.1126/scisignal.aan3398
Breger, Joyce C., Muttenthaler, Markus, Delehanty, James B., Thompson, Darren A., Oh, Eunkeu, Susumu, Kimihiro, Deschamps, Jeffrey R., Anderson, George P., Field, Lauren D., Walper, Scott A., Dawson, Philip E. and Medintz, Igor L. (2017) Nanoparticle cellular uptake by dendritic wedge peptides: achieving single peptide facilitated delivery. Nanoscale, 9 29: 10447-10464. doi:10.1039/c7nr03362a
Di Giglio, Maria Giulia , Muttenthaler, Markus, Harpsoe, Kasper, Liutkeviciute, Zita, Keov, Peter, Eder, Thomas, Rattei, Thomas, Arrowsmith, Sarah, Wray, Susan, Marek, Ales, Elbert, Tomas, Alewood, Paul F. , Gloriam, David E. and Gruber, Christian W. (2017) Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide. Scientific Reports, 7 1: 41002. doi:10.1038/srep41002
Synthesis of multivalent [Lys8]-oxytocin dendrimers that inhibit visceral nociceptive responses
Wan, Jingjing, Mobli, Mehdi, Brust, Andreas, Muttenthaler, Markus, Andersson, Asa, Ragnarsson, Lotten, Castro, Joel, Vetter, Irina, Huang, Johnny X., Nilsson, Mathias, Brierley, Stuart M., Cooper, Matthew A., Lewis, Richard J. and Alewood, Paul F. (2017) Synthesis of multivalent [Lys8]-oxytocin dendrimers that inhibit visceral nociceptive responses. Australian Journal of Chemistry, 70 2: 162-171. doi:10.1071/CH16407
Busnelli, Marta, Kleinau, Gunnar, Muttenthaler, Markus, Stoev, Stoytcho, Manning, Maurice, Bibic, Lucka, Howell, Lesley A., McCormick, Peter J., Di Lascio, Simona, Braida, Daniela, Sala, Mariaelvina, Rovati, G. Enrico, Bellini, Tommaso and Chini, Bice (2016) Design and characterization of superpotent bivalent ligands targeting oxytocin receptor dimers via a channel-like structure. Journal of Medicinal Chemistry, 59 15: 7152-7166. doi:10.1021/acs.jmedchem.6b00564
Muttenthaler, Markus, Albericio, Fernando and Dawson, Philip E. (2015) Methods, setup and safe handling for anhydrous hydrogen fluoride cleavage in Boc solid-phase peptide synthesis. Nature Protocols, 10 7: 1067-1083. doi:10.1038/nprot.2015.061
Arranz-Gibert, Pol, Guixer, Bernat, Malakoutikhah, Morteza, Muttenthaler, Markus, Guzman, Fanny, Teixido, Meritxell and Giralt, Ernest (2015) Lipid bilayer crossing-the gate of symmetry. Water-soluble phenylproline-based blood-brain barrier shuttles. Journal of the American Chemical Society, 137 23: 7357-7364. doi:10.1021/jacs.5b02050
Discovery, synthesis, and structure: activity relationships of conotoxins
Akondi, Kalyana, Muttenthaler, Markus, Dutertre, Sébastien, Kaas, Quentin, Craik, David J., Lewis, Richard J. and Alewood, Paul F. (2014) Discovery, synthesis, and structure: activity relationships of conotoxins. Chemical Reviews, Articles ASAP 11: 1-33. doi:10.1021/cr400401e
Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain
Dantas De Araujo, Aline, Mobli, Mehdi, Castro, Joel, Harrington, Andrea M., Vetter, Irina, Dekan, Zoltan, Muttenthale, Markus, Wan, JingJing, Lewis, Richard J., King, Glenn F., Brierley, Stuart M. and Alewood, Paul F. (2014) Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain. Nature Communications, 5 1: 3165.1-3165.12. doi:10.1038/ncomms4165
Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design
Koehbach, Johannes, O'Brien, Margaret, Muttenthaler, Markus, Miazzo, Marion, Akcan, Muharrem, Elliott, Alysha G., Daly, Norelle L., Harvey, Peta J., Arrowsmith, Sarah, Gunasekera, Sunithi, Smith, Terry J., Wray, Susan, Göransson, Ulf, Dawson, Philip E., Craik, David J., Freissmuth, Michael and Gruber, Christian W. (2013) Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design. Proceedings of the National Academy of Sciences of the United States of America, 110 52: 21183-21188. doi:10.1073/pnas.1311183110
Gemmill, Kelly Boeneman, Muttenthaler, Markus, Delehanty, James B., Stewart, Michael H., Susumu, Kimihiro, Dawson, Philip E. and Medintz, Igor L. (2013) Evaluation of diverse peptidyl motifs for cellular delivery of semiconductor quantum dots Optical Nanosensing in Cells. Analytical and Bioanalytical Chemistry, 405 19: 6145-6154. doi:10.1007/s00216-013-6982-2
Exploring bioactive peptides from natural sources for oxytocin and vasopressin drug discovery
Gruber, Christian W., Koehbach, Johannes and Muttenthaler, Markus (2012) Exploring bioactive peptides from natural sources for oxytocin and vasopressin drug discovery. Future Medicinal Chemistry, 4 14: 1791-1798. doi:10.4155/FMC.12.108
Muttenthaler, Markus, Dutertre, Sebastien, Wingerd, Joshua S., Aini, John W., Walton, Hugh, Alewood, Paul F. and Lewis, Richard J. (2012) Abundance and diversity of Conus species (Gastropoda: Conidae) at the northern tip of New Ireland province of Papua New Guinea. Nautilus, 126 2: 47-56.
Discovery of defense- and neuropeptides in social ants by genome-mining
Gruber, Christian W. and Muttenthaler, Markus (2012) Discovery of defense- and neuropeptides in social ants by genome-mining. PloS One, 7 3: e32559. doi:10.1371/journal.pone.0032559
Site-specific pKa determination of selenocysteine residues in selenovasopressin using 77Se NMR
Mobli, Mehdi, Morgenstern, David, King, Glenn F., Alewood, Paul F. and Muttenthaler, Markus (2011) Site-specific pKa determination of selenocysteine residues in selenovasopressin using 77Se NMR. Angewandte Chemie (International Edition), 50 50: 11952-11955. doi:10.1002/anie.201104169
Structure-activity studies on alpha-conotoxins
Muttenthaler, Markus, Akondi, Kalyana B. and Alewood, Paul F. (2011) Structure-activity studies on alpha-conotoxins. Current Pharmaceutical Design, 17 38: 4226-4241. doi:10.2174/138161211798999384
Modulating oxytocin activity and plasma stability by disulfide bond engineering
Muttenthaler, Markus, Andersson, Asa, Dantas de Araujo, Aline, Dekan, Zoltan, Lewis, Richard J. and Alewood, Paul F. (2010) Modulating oxytocin activity and plasma stability by disulfide bond engineering. Journal of Medicinal Chemistry, 53 24: 8585-8596. doi:10.1021/jm100989w
Gruber, Christian W., Muttenthaler, Markus and Freissmuth, Michael (2010) Ligand-based peptide design and combinatorial peptide libraries to target G protein-coupled receptors. Current Pharmaceutical Design, 16 28: 3071-3088. doi:10.2174/138161210793292474
Grishin, Anton, Wang, Ching-I. A., Muttenthaler, Markus, Alewood, Paul F., Lewis, Richard J. and Adams, David J. (2010) α-Conotoxin AuIB isomers exhibit distinct inhibitory mechanisms and differential sensitivity to stoichiometry of α3β4 nicotinic acetylcholine receptors. Journal of Biological Chemistry, 285 29: 22254-22263. doi:10.1074/jbc.M110.111880
Muttenthaler, Marcus, Nevin, Simon T., Grishin, Anton A., Ngo, Shyuan T., Choy, Peng T., Daly, Norelle L., Hu, Shu-Hong, Armishaw, Christopher J., Wang, Ching-I. A., Lewis, Richard J., Martin, Jennifer L., Noakes, Peter G., Craik, David J., Adams, David J. and Alewood, Paul F. (2010) Solving the alpha-conotoxin folding problem: Efficient selenium-directed on-resin generation of more potent and stable nicotinic acetylcholine receptor antaqonists. Journal of the American Chemical Society, 132 10: 3514-3522. doi:10.1021/ja910602h
Muttenthaler, Markus, Ramos, Yesica Garcia, Feytens, Debby, Dantas de Araujo, Aline and Alewood, Paul F. (2010) p-Nitrobenzyl protection for cysteine and selenocysteine: A more stable alternative to the acetamidomethyl group. Biopolymers, 94 4: 423-432. doi:10.1002/bip.21502
Muttenthaler, Markus and Alewood, Paul F. (2008) Selenopeptide chemistry. Journal of Peptide Science, 14 12: 1223-1239. doi:10.1002/psc.1075
Conopressin-T from Conus tulipa reveals an antagonist switch in vasopressin-like peptide
Dutertre, Sébastien, Croker, Daniel, Daly, Norelle L., Andersson, Åsa, Muttenthaler, Markus, Lumsden, Natalie G., Craik, David J., Alewood, Paul F., Guillon, Gilles and Lewis, Richard J. (2008) Conopressin-T from Conus tulipa reveals an antagonist switch in vasopressin-like peptide. Journal of Biological Chemistry, 283 11: 7100-7108. doi:10.1074/jbc.M706477200
Muttenthaler M., Bartel M., Weinberger P., Hilscher G. and Linert W. (2005) Synthesis and characterisation of new ditetrazole-ligands as more rigid building blocks of envisaged iron(II) spin-crossover coordination polymers. Journal of Molecular Structure, 741 1-3: 159-169. doi:10.1016/j.molstruc.2005.02.007
Arrowsmith, Sarah, Taylor, Olayisade, Muttenthaler, Markus and Wray, Susan (2016). Expression and function of vasopressin receptor subtypes in human myometrium: implications for effective tocolysis. In: Acta Physiologica. , , (21-22). .
Muttenthaler, Markus, Andersson, Asa, Ragnarsson, Lotten, Vetter, Irina, Busnelli, Marta, Chini, Bice, Arrowsmith, Sarah, Wray, Susan, de Araujo, Aline Dantas, Dutertre, Sebastien, Mobli, Mehdi, Lewis, Richard J., Gruber, Christian W. and Alewood, Paul F. (2016). Miklos Bodanszky Award Lecture Probing the Functional Complexity of Ancient Oxytocin in Health and Disease. In: Journal of Peptide Science. 34th European Peptide Symposium , Leipzig, Germany, (S7-S8). 4‐9 September 2016.
New pharmacological tools to investigate oxytocin receptors in neurodevelopmental brain disorders
Busnelli, M., Leonzino, M., Silva, B., Dona, E., Manning, M., Muttenthaler, M. and Chini, B. (2015). New pharmacological tools to investigate oxytocin receptors in neurodevelopmental brain disorders. In: Journal of Neurochemistry. 25th Biennial Meeting of the International-Society-for-Neurochemistry Jointly with the 13th Meeting of the Asian-Pacific-Society-for-Neurochemistry in Conjunction with the 35th Meeting of the Australasian-Neuroscience-Society, Cairns Australia, (168-168). Aug 23-27, 2015.
Re-Examining the Importance of Vasopressin Receptors in Myometrial Contraction.
Arrowsmith, Sarah, Wray, Susan and Muttenthaler, Markus (2015). Re-Examining the Importance of Vasopressin Receptors in Myometrial Contraction.. In: Reproductive Sciences. , , (332A-332A). .
Insights into the molecular evolution of oxytocin receptor ligand binding
Koehbach, Johannes, Stockner, Thomas, Bergmayr, Christian, Muttenthaler, Markus and Gruber, Christian W. (2013) Insights into the molecular evolution of oxytocin receptor ligand binding. Biochemical Society Transactions, 41 1: 197-204. doi:10.1042/BST20120256
Peptide-mediated cellular delivery of semiconductor quantum dots
Gemmill, K.B., Muttenthaler, M., Delehanty, J., Deschamps, J., Susumu, K., Stewart, M., Dawson, P., Huston, A. and Medintz, I. (2013). Peptide-mediated cellular delivery of semiconductor quantum dots. In: Šárka O. Southern, Conference on Sensing Technologies for Global Health, Military Medicine, and Environmental Monitoring III, Baltimore, United States, (). Apr 29-May 01, 2013. doi:10.1117/12.2015446
Novel sources for potent and selective GPCR modulators
Muttenthaler, M., Dawson, P. E., Gruber, C. W., Bergmayr, C., Freissmuth, M., Andersson, A., Vetter, I., Dutertre, S., Lewis, R. J. and Alewood, P. F. (2012). Novel sources for potent and selective GPCR modulators. In: unknown, unknown, (S26-S26). unknown. doi:10.1002/psc.2447
Pharmacological characterization of circular plant peptides with oxytocin-like activity
Koehbach, J., O'Brien, M., Miazzo, M., Muttenthaler, M., Akcan, M., Smith, T. J., Craik, D. J., Freissmuth, M. and Gruber, C. W. (2012). Pharmacological characterization of circular plant peptides with oxytocin-like activity. In: Proceedings of the 32nd European Peptide Symposium. 32nd European Peptide Symposium "Peptides 2012", Athens, Greece, (S98-S98). 02-07 September 2012. doi:10.1002/psc.2449
Conotoxins - blueprints for GPCR drug discovery?
Muttenthaler, M., Gruber, C. W., Andersson, A., Vetter, I., Nevin, S. T., Grishin, A. A., Dutertre, S., Daly, N. L., Craik, D. J., Adams, D. J., Lewis, R. J. and Alewood, P. F. (2011). Conotoxins - blueprints for GPCR drug discovery?. In: 22nd American Peptide Symposium, San Diego, CA, United States, (422-422). 25-30 June 2011.
Muttenthaler, M. M., de Araujo, A. D., Andersson, A., Vetter, I., Gruber, C., Ramos, Y. Garcia, Feytens, D., Bergmayr, C., Freissmuth, M., Lewis, R. and Alewood, P. (2010). Oxytocin agonist design - A selenocysteine mimetic reveals a functional selectivity switch for the human oxytocin receptor. In: Journal of Peptide Science. 31st European Peptide Symposium, Copenhagen, Denmark, (161-161). 5-9 September 2010. doi:10.1002/psc.1303
Selenocysteine in peptide drug design
Adams, D. J., Alewood, P. F., Choy, P. T., Craik, D. J., Daly, N. L., Grishin, A. A., Hu, S-H., Martin, J. L., Muttenthaler, M., Nevin, S. T., Ngo, S. T. and Noakes, P. G. (2008). Selenocysteine in peptide drug design. In: Royal Australian Chemical Institute (RACI) Annual Scientific Meeting: Drug Discovery and Development, Couran Cove Island Resort, Queensland, Australia, (). 13 - 17 July 2008.
Selenocysteine in peptide folding and drug design
Muttenthaler, M., Nevin, S. T., Grishin, A. A., Ngo, S. T., Choy, P. T., Daly, N. L., Hu, S-H., Martin, J. L., Noakes, P. G., Craik, D. J., Adams, D. J. and Alewood, P. F. (2008). Selenocysteine in peptide folding and drug design. In: XXth International Symposium on Medicinal Chemistry (EFMC-ISMC 2008), Vienna, Austria, (). 31 August - 4 September 2008.
Directed folding of alpha-conotoxins using selenocysteine
Muttenthaler, M. and Alewood, P. F. (2006). Directed folding of alpha-conotoxins using selenocysteine. In: Journal Of Peptide Science. 29th European Peptide Symposium. 29th European Peptide Symposium, Gdansk, Poland, (87-87). 3-8 September 2006. doi:10.1002/psc.796
Aquatic chemo-modulators - a novel source for potent molecular probes
(2019–2021) ARC Discovery Projects
(2019) UQ Major Equipment and Infrastructure
In vivo imaging system for tracking inflammation, infection, cancer, pain and bioactive molecules
(2019) UQ Major Equipment and Infrastructure
Development of oxytocin receptor specific tracers for improved breast cancer management
(2018–2021) Cancer Australia
Development of oxytocin receptor specific tracers for improved breast cancer management
(2018–2019) Cancer Council Queensland
(2018) UQ Major Equipment and Infrastructure
Novel therapeutic approaches to improve gastrointestinal wound healing - GUTPEPTIDES
(2017–2021) University of Vienna
(2017–2020) University of Sydney
Gastrointestinal wound healing as a therapeutic approach to treat gastrointestinal disorders
(2016–2018) UniQuest Pty Ltd
Mapping the location and function of oxytocin and vasopressin receptors throughout the gut
(2016–2018) Ferring Research Institute
Intranasal Oxytocin - does it reach the central nervous system ?
(2016–2017) UQ Early Career Researcher
Individual function and social role of oxytocin-like neuropeptides in ants
(2014–2017) Medical University of Vienna
Development of human trefoil factor 3 probes via structure and activity relationship study
Doctor Philosophy — Principal Advisor
Other advisors:
Development of oxytocin receptor-specific tracers for breast tumour detection
Doctor Philosophy — Principal Advisor
Other advisors:
Exploring the oxytocin receptor as a novel target for breast tumour inhibition
Doctor Philosophy — Principal Advisor
Other advisors:
Development of receptorsubtype selective probes to study the oxytocin and vasopressin signalling system in disease
Doctor Philosophy — Principal Advisor
Other advisors:
Novel therapeutic approaches to improve gastrointestinal wound healing
Doctor Philosophy — Associate Advisor
Other advisors:
Investigation of the venom of the Estuarine Stonefish, Synanceia horrida
Doctor Philosophy — Associate Advisor
Other advisors:
Animal venom drug discovery
Doctor Philosophy — Associate Advisor
Other advisors:
Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.
Oxytocin and Vasopressin Research
Please contact Dr Muttenthaler directly for further details
Venom peptide drug discovery
Please contact Dr Muttenthaler directly for further details.
Breast Cancer
Please contact Dr Muttenthaler directly for further details.
Ligand design and chemical synthesis
Project for interns or summer student.
Please contact Dr Muttenthaler directly for further details.
Gastrointestinal wound healing
Please contact Dr Muttenthaler directly for further details.
Tracer development for PET/MRI applications
Structure-activity relationship studies of human neuropeptides