Transcript University of Wollongong - Research Network for Metals in Medicine

Metals in Medicine Research
University of Wollongong
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Institute for Biomolecular
Science (IBS)
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Project areas include:
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14 Academic Staff
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Dept. of Chemistry
Dept. of Biology
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9 Postdocs
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30 PhD Students
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B. Med Chem
B. Biotech
Drug design and
development
Biomolecular structure
determination
Cellular and molecular
biology
Food and natural product
chemistry
Mechanism of cataract
formation
Interactions of Gold Drugs with
Proteins
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O2C CH2
H
C
H
Au S
CO2-
CH2
Au S
(n)
Myochrysin
CH2OAc
O
OAc
OAc
OAc
Auranofin
HC
OH
CH2
SO3Na
(n)
Allochyrsine
S
Au PEt3
How does Chrysotherapy Work?
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Many possible mechanisms of action:
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Anti-inflammatory
Inhibition of lysosomal enzymes
Immunomodulatory activity
Effects on metabolism of reactive oxygen
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All gold drugs rapidly bind to proteins containing thiol
side chains, but not DNA.
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[Au(CN)2]- is a common metabolite of all Au drugs
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Au(I) oxidised to Au(III) in vivo
ESI-MS of Human Serum Albumin (HSA)
J. Croft, CHEM340, 2004
Reaction between [Au(PEt3)Cl] and
Metallothionein
S. Ambehara, B.Sc(Hons), 20002
Covalent Binding of Ruthenium
Compounds to DNA
J. Torrens, B.Sc(Hons), 2000
Non-covalent Interactions Between
Ruthenium Complexes and DNA
2
N
N
N
N
N
N
N
N
Ru
N
N
N
N
N
N
N
[Ru(phen) 2(dpq)] 2+
2
N
N
N
N
CH3
N
N
N
N
N
N
N
Ru
Ru
N
[Ru(phen) 2(pda) ]2+
2
2
N
N
N
N
N
[Ru(phen) 3]2+
N
Ru
Ru
N
N
2
2
N
N
CH3
[Ru(phen) 2(dpqMe 2)]2+
[Ru(phen) 2(dpqC)] 2+
J. Aldrich-Wright and co-workers
N
N
N
Ru
N
N
N
N
[Ru(phen) 2(dppz)] 2+
ESI-MS of D2
[D2-6H]6-
[D2-5H]5-
T. Urathamakul, B.Sc(Hons), 2002
ESI-MS of [Ru(phen)2(dpqC)]2+
(mol. wt = 748)
T. Urathamakul, B.Sc(Hons), 2002
Reactions between [Ru(phen)3]2+ and
D2
T. Urathamakul, B.Sc(Hons), 2002
Ru:D2 = 5:1
Ru:D2 = 10:1
Ru:D2 = 20:1
Ru:D2 = 30:1
Ru:D2 = 50:1
L = phen
L = pda
L = dpq
Reactions between
[Ru(phen)2L]2+
and D2
T. Urathamakul
B.Sc(Hons), 2002
L = dpqMe2
L = dpqC
L = dppz
Future Work
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Binding of mono- and
poly-nuclear ruthenium
complexes to longer DNA
and DNA containing other
base sequences
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Binding of gold,
vanadium, bismuth,
ruthenium and other
metal-containing drugs to
proteins including HSA,
MT and Transferrin