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NMR Studies of Second Generation Polynuclear Platinum Compounds. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these ne ....NMR Studies of Second Generation Polynuclear Platinum Compounds. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these new drugs puts Australian research at the forefront of the clinical development. There is the potential for the generation of new IP from new strategies in the design of improved anticancer drugs. The project builds strong international links and provides international training for Australian PhD students.Read moreRead less
Special Research Initiatives - Grant ID: SR0354474
Funder
Australian Research Council
Funding Amount
$30,000.00
Summary
Metals in Medicine. Metal-based drugs account for several billion dollars of pharmaceutical sales worldwide, but proportionally much less research and development has focussed on this area than organic drugs. Australia has played a pivotal role in the early development of metal-based pharmaceuticals, which remains a research strength. The dual aims of the initiative are to provide a network for a vibrant industry based around metals in medicine and to improve the health of Australians. The ini ....Metals in Medicine. Metal-based drugs account for several billion dollars of pharmaceutical sales worldwide, but proportionally much less research and development has focussed on this area than organic drugs. Australia has played a pivotal role in the early development of metal-based pharmaceuticals, which remains a research strength. The dual aims of the initiative are to provide a network for a vibrant industry based around metals in medicine and to improve the health of Australians. The initiative will foster national and international cross-disciplinary collaborations to address the impediments holding back Australia's potential to take full advantage of our research strength in metals in medicine.Read moreRead less
Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. ....Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. Using the combined expertise of the applicants, it is proposed to stereospecifically synthesise dinuclear complexes and study their DNA binding. This will greatly assist in the development of drugs that can selectively target genes and altered DNA.Read moreRead less
The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to c ....The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to clinical observations regarding dietary intake of selenium and other compounds. The new understanding generated will delineate the conditions for safe intake, so that the beneficial effects associated with selenium supplementation may be harnessed more effectively.Read moreRead less
Microprobe and Nanoprobe Studies on Intracellular Disease Processes and Their Treatment. Breakthrough microprobe and nanoprobe technologies, involving X-ray, visible and infrared light can focus into different components of mammalian cells in order to interrogate the biochemistry that is occurring therein. Each of the different wavelengths of light provides complementary biochemical information that enables a deeper understanding of changes in cells that occur as a function of drug treatments an ....Microprobe and Nanoprobe Studies on Intracellular Disease Processes and Their Treatment. Breakthrough microprobe and nanoprobe technologies, involving X-ray, visible and infrared light can focus into different components of mammalian cells in order to interrogate the biochemistry that is occurring therein. Each of the different wavelengths of light provides complementary biochemical information that enables a deeper understanding of changes in cells that occur as a function of drug treatments and disease processes. This will provide unprecedented information as to where drugs go and how they are transformed inside cells that, in turn, may revolutionalise the way in which new drugs are designed that have higher specificity and fewer side effects.Read moreRead less
Structure-based design of anti-osteoporotic drug leads: an integrated approach. One of the major consequences of Australia's aging population is that age-related diseases, such as osteoporosis, are increasing. Apart from the significant human suffering caused by this disease, there is an immense financial burden on the community, patients and their families. Current treatments for osteoporosis are often ineffective and also have major side-effects. An enzyme has been identified which plays a cru ....Structure-based design of anti-osteoporotic drug leads: an integrated approach. One of the major consequences of Australia's aging population is that age-related diseases, such as osteoporosis, are increasing. Apart from the significant human suffering caused by this disease, there is an immense financial burden on the community, patients and their families. Current treatments for osteoporosis are often ineffective and also have major side-effects. An enzyme has been identified which plays a crucial role in the progression of this disease by increasing the rate of bone-thinning. We will make compounds to slow down this enzyme. This project will provide the basis for the future development of new and improved drugs to treat osteoporosis.Read moreRead less
Development of metal probes for the selective recognition of DNA. Transition metal complexes with large aromatic ligands have recently been shown to bind DNA by intercalation. However, controversy continues over their base sequence and groove selectivity. We will synthesise a range of chiral metal complexes and screen these against combinatorial oligonucleotide libraries to determine their base sequence selectivity. The information obtained will help us design better intercalators that can be us ....Development of metal probes for the selective recognition of DNA. Transition metal complexes with large aromatic ligands have recently been shown to bind DNA by intercalation. However, controversy continues over their base sequence and groove selectivity. We will synthesise a range of chiral metal complexes and screen these against combinatorial oligonucleotide libraries to determine their base sequence selectivity. The information obtained will help us design better intercalators that can be used as sensitive molecular probes and may find application as antitumour drugs. Binding interaction between the complex and DNA will be studied by NMR spectroscopy.Read moreRead less
Development of New Materials Based on Multinuclear Ruthenium Complexes. The program aims to design new materials for use in applications such as catalysis and light-activated devices (including light harvesting or solar energy conversion), for the detection and analysis of specific small molecules and anions of particular interest, and to provide an insight to the operation of biological systems such as metal-containing enzymes. The particular molecules will also be investigated for the developm ....Development of New Materials Based on Multinuclear Ruthenium Complexes. The program aims to design new materials for use in applications such as catalysis and light-activated devices (including light harvesting or solar energy conversion), for the detection and analysis of specific small molecules and anions of particular interest, and to provide an insight to the operation of biological systems such as metal-containing enzymes. The particular molecules will also be investigated for the development of a new type of therapeutic agent for the treatment of a range of diseases, with a particular interest in this work on a drug for the treatment of HIV-AIDS. Read moreRead less
Experimental Charge Density Studies of Hydrogen Bonding. Hydrogen bonds, vital to all biological systems, exhibit extreme variation in chemical properties. Experimental analysis of hydrogen bonds, independent from previous theories and hypotheses, by using an expansion of current high resolution, ultra-low temperature X-ray crystallography is now possible. This allows experimental observation of electronic and electrostatic properties of previously unstudied hydrogen bonds, including weak hydrog ....Experimental Charge Density Studies of Hydrogen Bonding. Hydrogen bonds, vital to all biological systems, exhibit extreme variation in chemical properties. Experimental analysis of hydrogen bonds, independent from previous theories and hypotheses, by using an expansion of current high resolution, ultra-low temperature X-ray crystallography is now possible. This allows experimental observation of electronic and electrostatic properties of previously unstudied hydrogen bonds, including weak hydrogen bonds and those involving metal atoms. Comparison of experimental observations with predictions from high-level theoretical calculations and finally incorporation of these parameters into a prototype force field for computational chemistry will allow better predictions to be made in a range of areas including medicinal and materials chemistry.Read moreRead less
DNA interactions of polynuclear platinum. Mechanistic NMR studies probing the origin of the unique antitumour activity of BBR3464. BBR3464 is one of a class of structurally unique platinum anticancer drugs that is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is quite different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow the processes involved in the initial binding of the dr ....DNA interactions of polynuclear platinum. Mechanistic NMR studies probing the origin of the unique antitumour activity of BBR3464. BBR3464 is one of a class of structurally unique platinum anticancer drugs that is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is quite different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow the processes involved in the initial binding of the drug to DNA and the subsequent reactions of the adducts formed. The results of this work will aid in the selection of back-up clinical candidates and in the design of drugs that target specific sequences of DNA for use in novel gene-based therapies.Read moreRead less