Metals in Medicine Research University of Wollongong Institute for Biomolecular Science (IBS) Institute for Biomolecular Science (IBS) 14 Academic Staff 14 Academic Staff Dept. of Chemistry Dept. of Chemistry Dept. of Biology Dept. of Biology 9 Postdocs 9 Postdocs 30 PhD Students 30 PhD Students B. Med Chem B. Med Chem B. Biotech B. Biotech Project areas include: 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

How does Chrysotherapy Work? Many possible mechanisms of action: Many possible mechanisms of action: Anti-inflammatory Anti-inflammatory Inhibition of lysosomal enzymes Inhibition of lysosomal enzymes Immunomodulatory activity Immunomodulatory activity Effects on metabolism of reactive oxygen Effects on metabolism of reactive oxygen All gold drugs rapidly bind to proteins containing thiol side chains, but not DNA. All gold drugs rapidly bind to proteins containing thiol side chains, but not DNA. [Au(CN) 2 ] - is a common metabolite of all Au drugs [Au(CN) 2 ] - is a common metabolite of all Au drugs Au(I) oxidised to Au(III) in vivo Au(I) oxidised to Au(III) in vivo

ESI-MS of Human Serum Albumin (HSA) J. Croft, CHEM340, 2004

Reaction between [Au(PEt 3 )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 J. Aldrich-Wright and co-workers

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 Ru:D2 = 5:1 Ru:D2 = 10:1 Ru:D2 = 20:1 Ru:D2 = 30:1 Ru:D2 = 50:1 T. Urathamakul, B.Sc(Hons), 2002

Reactions between [Ru(phen) 2 L] 2+ and D2 L = phen L = pda L = dpq L = dpqMe 2 L = dpqC L = dppz T. Urathamakul B.Sc(Hons), 2002 B.Sc(Hons), 2002

Future Work Binding of mono- and poly-nuclear ruthenium complexes to longer DNA and DNA containing other base sequences Binding of mono- and poly-nuclear ruthenium complexes to longer DNA and DNA containing other base sequences Binding of gold, vanadium, bismuth, ruthenium and other metal-containing drugs to proteins including HSA, MT and Transferrin Binding of gold, vanadium, bismuth, ruthenium and other metal-containing drugs to proteins including HSA, MT and Transferrin