<b>Professor Paul Alewood</b><br>
Laboratory Head, Chemistry and Structural Biology Division<br><p>
P: +61 7 3346 2982<br>
E: p.alewood@imb.uq.edu.au<p>
<b>Keywords</b><br>
- chronic pain<br>
- irritable bowel syndrome<br>
- breast cancer<br>
- inflammation<br>
- congestive heart failure<br>
- insecticides<br>
- drug discovery<br>
- drug development
Professor Paul Alewood
Laboratory Head, Chemistry and Structural Biology Division

P: +61 7 3346 2982
E: p.alewood@imb.uq.edu.au

Keywords
- chronic pain
- irritable bowel syndrome
- breast cancer
- inflammation
- congestive heart failure
- insecticides
- drug discovery
- drug development

Visit the Alewood Lab website for more information.

Design and discovery of bioactive peptides and proteins in venomous animals

 

Our research focuses on identifies and develops bioactive molecules from Australia’s venomous animals that have the potential to create treatments for chronic pain, heart disease, inflammation, irritable bowel syndrome, and breast cancer.
Although toxins from these animals can have a devastating effect, molecules within them have been found to be useful in treating human disease. Specifically, we are interested in the discovery and total synthesis of potent and selective peptides (toxins) from venomous animals, and their development into therapeutic candidates to treat a range of diseases.

Recently, our lab has investigated druggable receptors in the gut, and ways to reduce protease degradation and disulfide bond rearrangements in drug candidates. Our lab recently described a mouse model of chronic abdominal pain where oxytocin receptors are significantly upregulated in nociceptors (pain receptors) without affecting normal tissue, which is an important advantage in drug development.

During the past 12 months, we developed novel chemical strategies to engineer non-reducible and more stable oxytocin analogues, which may be developed as treatments for irritable bowel syndrome. Chemoselective selenide macrocyclisation yielded stabilised analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives revealed that oxytocin has a pre-organised structure in solution, in marked contrast to earlier X-ray crystallography studies.

Finally, we showed that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity, which mostly affects the gut. This research has important implications for clinical use of oxytocin analogues and cysteine-rich peptides in general.

 

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Student projects and opportunities

View current Alewood Lab honours projects.

Key publications

View more publications by Professor Alewood via PubMed.

Muttenthaler, M., Nevin, S.T., Grishin, A.A., Ngo, S.T., Choy, P.T., Daly, N.L., Hu, S-H., Armishaw, C.J., Wang, C.I.A., Lewis, R.J., Martin, J.L., Noakes, P.G., Craik, D.J., Adams, D.J., and Alewood, P.F. (2010). Solving the α-conotoxin folding problem: selenium-directed on-resin generation of more potent and stable nicotinic acetylcholine receptor antagonists. Journal of the American Chemistry Society 132: 3514-3522.

Morales, R.A.V., Daly, N.L., Vetter, I., Mobli, M., Napier, I.A., Craik, D.J., Lewis, R.J., Christie, M.J., King, G.F., Alewood, P.F., and Durek, T. (2010). Total chemical Synthesis and Structure of the Prokineticin Bv8. Chembiochem 11: 1882-1888.

Beatrix, M., Ueberheide, D.F., Alewood, P.F., and Chait, B.T. (2009). Rapid, sensitive analysis of cysteine rich peptide venom components. Proceedings of the National Academy of Sciences USA 106: 6910-6915.

Brust, A., Palant, E., Croker, D.E., Colless, B., Drinkwater, R., Patterson, B., Schroeder, C.L., Wilson, D., Nielsen, C.K., Smith, M.T., Alewood, D., Alewood, P.F., and Lewis, R.J. (2009). Chi-conopeptides Pharmacophore Development: Towards a novel class of Norepinephrine Transporter Inhibitor (Xen2174) for Pain. Journal of Medicinal Chemistry 52: 6991-7002.

Vernall, A.J., Cassidy, P., and Alewood, P.F. (2009). A single alpha-helical turn stabilized by replacement of an internal hydrogen bond with a covalent ethylene bridge. Angewandte Chemistry International Edition 48: 5675-5678.

Lab contacts

 

Professor Paul Alewood
Laboratory head
+61 7 334 62982
p.alewood@imb.uq.edu.au
Dr AiHua (Jean) Jin
Research staff
+61 7 334 62985
a.jin@imb.uq.edu.au
 Mr Tim Reeks
Research higher degree student
+61 7 334 62377
t.reeks@imb.uq.edu.au
Dr Andreas Brust
Research staff
+61 7 334 62377
a.brust@imb.uq.edu.au
Mr Vincent Lavergne
Research higher degree student
+61 7 334 62377
v.lavergne@imb.uq.edu.au
Ms Jingjing Wan
Research higher degree student
+61 7 334 62377
j.wan@imb.uq.edu.au
Mr Zoltan Dekan
Research staff
+61 7 334 62377
z.dekan@imb.uq.edu.au