2010 Annual Report - Institute for Molecular Bioscience - University ...

imb annual report 2010
52
PAUL ALEWOOD
DESIGN AND DISCOVERY OF BIOACTIVE PEPTIDES
AND PROTEINS
THE OVERALL FOCUS IN THE
group www.uq.edu.au/alewood/ is the
identification of bioactive molecules that
have the potential to play important roles
in human health and wellbeing. Some
specific interests include: the discovery
and total synthesis of potent and selective
peptides (toxins) from Australia’s venomous
creatures; the chemical synthesis of
proteins and bioactive peptides; the
development of new synthetic and
analytical chemistry; and protein structure
and function. Special emphasis is placed
on determining the structure-function
relationships of natural and designed
molecules. Current research programs
involve: the discovery, isolation and
characterisation of toxins from snakes,
spiders, cone snails, platypus, ticks and
scorpions; mimetics of calcium-binding
inflammatory proteins from the S100 class;
the chemical engineering of disulfide-rich
peptides and proteases; elucidating the
structure and function of milk proteins and
their role in human health; and uncovering
new pain pathways in chronic pain.
RESEARCH PROJECTS
• Identification and characterisation of
novel peptides from Australian animals
that target ion channels, transporters
and GPCR receptors
• Dissecting chronic neuropathic pain
pathways with receptor-selective toxins
• Protein mimetics
• Development of new enabling synthetic
chemistry to access disulfide-rich
peptides and small bioactive proteins
and enzymes (up to 200 residues)
• Design and synthesis of novel small
molecules that mimic peptide structure
and function (peptidomimetics)
KEY PUBLICATIONS
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.
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 a-conotoxin folding problem:
selenium-directed on-resin generation
of more potent and stable nicotinic
acetylcholine receptor antagonists. Journal
of the American Chemical Society 132:
3514-3522.
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 a-helical turn stabilized
by replacement of an internal hydrogenbond
with a covalent ethylene bridge.
Angewandte Chemie International Edition
48: 5675-5678.
Sharpe, I., Gehrmann, J., Loughnan,
M., Thomas, L., Adams, D., Atkins, A.,
Craik, D.J., Adams, D., Alewood, P.F.,
and Lewis, R.J. (2001). Two new classes
of conopeptides inhibit the alpha1-
adrenoceptor and the noradrenaline
transporter. Nature Neuroscience 4: 902-
907.
LAB MEMBERS
Senior Research Officers: Dr John
Holland, Dr Lachlan Rash, Dr Andreas
Brust
Research Officers: Dr Aline Dantas,
Dr Tom Durek, Dr Jean Jin, Dr Markus
Muttenthaler
Research Assistant: Zoltan Dekan
PhD Students: Rod Morales, Jen Smith,
Kalyani Akondi, Simone Vink, Vincent
Lavergne
Visiting Students: Soren Langer
(University of Copenhagen), Louise Anker
(University of Copenhagen), Claudia
Hjørringgård (Aarhus University, Denmark)