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

53 imb researchers: chemistry and structural biology
ROB CAPON
BIODISCOVERY: PATHWAYS TO NEW BIOACTIVE
CHEMICAL DIVERSITY
disulfide and only the second known
natural nucleoside to incorporate a xylose
sugar residue.
Heronapyrroles: the first reported natural
examples of nitropyrroles, and a new class
of Gram +ve selective antibacterials (target
– antibiotics).
Ircinialactams: new examples of a rare class
of terpenyl glycinyl-lactams, and the first
reported isoform selective potentiators of
GlyR (target – chronic inflammatory pain).
MY RESEARCH GROUP EXPLORES
the chemical diversity of Australian plants,
animals and microbes as a source of novel
products to (i) advance our knowledge
of the natural world, (ii) provide insights
into chemical ecology to assist in the
control of invasive pests, and (iii) inspire
the development of new pharmaceuticals,
agrochemicals and bioprobes. These
investigations require the use and
continued refinement of sophisticated
chromatographic (HPLC-DAD-ELSD),
spectroscopic (NMR, MS) and chemical
(synthesis, degradation, derivatisation,
biotransformation) technologies,
supported by a wide array of innovative
bioassays aimed at multiple targets
across such indications as infectious and
neurodegenerative disease, pain, cancer
and diabetes. Metabolites encountered
during our studies span all biosynthetic
pathways, feature unprecedented carbon
skeletons, heterocycles and functional
groups, and can possess potent and
selective biological properties with high
value across basic and applied science.
Recent examples include:
Franklinolides: the first reported natural
example of a polyketide-phosphodiester,
with an exceptional enhancement in
cytotoxicity (target - cancer).
Heterofibrins: the first reported natural
examples of lactyl-lipid esters and a new
class of lipid droplet inhibitor (target -
obesity, atherosclerosis and diabetes).
Nocardiopsins: the first reported natural
examples of the rapamycin class to be
described in over a decade (target -
immunosuppressive agents).
5’-Xyloadenosine Disulfide: the first
reported natural example of a nucleoside
KEY PUBLICATIONS
Zhang, H., Conte, M.M., and Capon,
R.J. (2010). Franklinolides A-C from
an Australian marine sponge complex:
Phosphodiesters dramatically enhance
polyketide cytotoxicity. Angewandte
Chemie International Edition 122: 1-4.
Salim, A.A., Rae, J., Fontaine, F., Conte,
M.M., Khalil, Z., Martin, S., Parton, R.G.,
and Capon, R.J. (2010). Heterofibrins:
Inhibitors of lipid droplet formation from
a deep-water southern Australian marine
sponge, Spongia (Heterofibria) sp.
Organic and Biomolecular Chemistry 8:
3188-3194.
Raju, R., Piggott, A.M., Conte, M.,
Tnimov, Z., Alexandrov, K., and Capon,
R.J. (2010). Nocardiopsins: New FKBP12-
binding macrolide polyketides from an
Australian marine-derived actinomycete,
Nocardiopsis sp. Chemistry: A European
Journal 16: 3194-3200.
Peng, C., Gunaherath, G.M.K.B., Piggott,
A.M., Khalil, Z., Conte, M., and Capon,
R.J. (2010). 9-(5’-Deoxy-5’-thio-β-Dxylofuranosyl)
adenine disulfide from
the southern Australian marine sponge
Trachycladus lasvispirulifer: The first
natural occurrence of a nucleoside
disulfide. Australian Journal of Chemistry
63: 873-876.
Raju, R., Piggott, A.M., Barrientos Diaz,
L.X., Khalil, Z., and Capon, R.J. (2010).
Heronapyrroles A-C: Farnesylated
2-nitropyrroles from an Australian marinederived
Streptomyces sp. Organic Letters
12: 5158-5161.
Balansa, W., Islam, R., Fontaine, F.,
Piggott, A.M., Zhang, H., Webb, T.I.,
Gilbert, D.F., Lynch, J.W., and Capon,
R.J. (2010). Ircinialactams: Subunitselective
glycine receptor modulators from
Australian sponges of the family Irciniidae.
Bioorganic & Medicinal Chemistry 18:
2912-2919.
Raju, R., Piggott, A.M., Conte, M.M., and
Capon, R.J. (2010). Heronamides A-C,
new polyketide macrolactams from an
Australian marine-derived Streptomyces
sp. A biosynthetic case for synchronized
tandem electrocyclization. Organic and
Biomolecular Chemistry 8: 4682-4689.
Capon, R.J. (2010). Marine natural
products chemistry: Past, present, and
future. Australian Journal of Chemistry 63:
851-854.
Raju, R., Piggott, A.M., Conte, M.,
Aalbersberg, W.G.L., Feussner, K., and
Capon, R.J. (2010). Naseseazines A-B: A
new dimeric diketopiperazine framework
from a marine-derived actinomycete,
Steptomyces sp. Organic Letters 11:
3862-3865.
Hayes, R.A., Piggott, A.M., Dalle, K.,
and Capon, R.J. (2010). Microbial
biotransformation as a source of chemical
diversity in cane toad steroid toxins.
Bioorganic and Medicinal Chemistry
Letters 19: 1790-1792.
LAB MEMBERS
Personal Assistant: Naomi Epstein
Research Officers: Dr Angela Salim, Dr
Andrew Piggott, Dr Hua Zhang, Dr Sean
Xiao
PhD Students: Walter Balansa, Raju
Ritesh, Soumini Vijayasarathy, Fabien
Plisson, Zeinab Khalil, Victor Huang,
Venkat Kamalakkannan
Undergraduate Students: Siti Zulkifli,
Angel Koo, Ahmad Bin Rosli, Kylie James
International Occupational Trainee:
Olusegun Ajala (Nigeria)
International Visiting Scientists: Fuhang
Song (China), Leticia Barrentos Diaz
(Chile)