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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
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
Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug ta ....Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug targets. This research will lead to new strategies in the design of improved anticancer drugs, which is an important Australian research priority that will promote and maintain good health, and provide potential commercial outcomes.Read moreRead less
Probing polynuclear platinum biomolecule interactions. 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 with the inventor of these new drugs puts Australian research at t ....Probing polynuclear platinum biomolecule interactions. 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 with 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
Gold-based mitochondria targeted chemotherapeutics: mechanistic studies probing interactions with thiol and selenol containing proteins. Cancer affects one in four Australians and prostate cancer is the most commonly diagnosed and second leading cause of male cancer deaths, for which there is currently no effective treatment. Current chemotherapeutics must overcome drug resistance and lack of selectivity between tumour and normal cells. To circumvent these problems we are investigating gold-base ....Gold-based mitochondria targeted chemotherapeutics: mechanistic studies probing interactions with thiol and selenol containing proteins. Cancer affects one in four Australians and prostate cancer is the most commonly diagnosed and second leading cause of male cancer deaths, for which there is currently no effective treatment. Current chemotherapeutics must overcome drug resistance and lack of selectivity between tumour and normal cells. To circumvent these problems we are investigating gold-based compounds, which act by a novel mechanism. The research will lead to new strategies in the design of improved anticancer drugs, an important Australian research priority that will promote and maintain good health. Other benefits arise from training PhD students with interdisciplinary skills for Australian biotechnology industries.Read moreRead less
Second Generation Polynuclear Platinum Compounds. Mechanistic NMR Studies Probing DNA Binding and Pharmacokinetics. 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 betwe ....Second Generation Polynuclear Platinum Compounds. Mechanistic NMR Studies Probing DNA Binding and Pharmacokinetics. 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
NMR studies on DNA interactions of polynuclear platinum. BBR3464 is representative of a class of structurally unique platinum anticancer drugs, and is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow in detail the stepwise formation of DNA adducts. Further extension to reactions of polynuclear platinum complexes with sulfur ....NMR studies on DNA interactions of polynuclear platinum. BBR3464 is representative of a class of structurally unique platinum anticancer drugs, and is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow in detail the stepwise formation of DNA adducts. Further extension to reactions of polynuclear platinum complexes with sulfur nucleophiles will aid in understanding their metabolism and toxicity. The results of this work will aid in the selection of back-up clinical candidates and the design of drugs that target specific sequences of DNA for use in novel gene-based therapies.Read moreRead less
Ferrihydrite : Fundamentals of a Natural Nanomaterial. The overarching goal of this project is to obtain the depth of knowledge necessary to achieve specific size, composition and morphology control in the crystallization of nanometer-sized iron oxides. The project focusses on the structural characteristics of the oxy-hydroxide phase ferrihydrite, which is a key intermediate in the formation of other iron oxides. The project will employ characterization techniques such as small-angle scattering ....Ferrihydrite : Fundamentals of a Natural Nanomaterial. The overarching goal of this project is to obtain the depth of knowledge necessary to achieve specific size, composition and morphology control in the crystallization of nanometer-sized iron oxides. The project focusses on the structural characteristics of the oxy-hydroxide phase ferrihydrite, which is a key intermediate in the formation of other iron oxides. The project will employ characterization techniques such as small-angle scattering, high resolution TEM, electron nanodiffraction and magnetic energy barrier distribution measurements to study crystallization processes of the iron oxy-hydroxide ferrihydrite, both in vivo and in vitro. The knowledge gained from the biological realm will allow us to devise new laboratory techniques for the preparation of nanoparticles, and provide important information about iron biomineralization to advance the treatment of iron overload diseases.Read moreRead less
Gold phosphine and carbene complexes as potential antimitochondrial anticancer agents: design, synthesis and biological chemistry. To overcome the two major problems associated with existing anticancer drugs (resistance to therapy and lack of discrimination between normal and cancer cells) there is much current interest in targeting mitochondrial cell death pathways in chemotherapy. This project will probe the mode of action of a series of gold complexes containing pyridylphosphines that may ac ....Gold phosphine and carbene complexes as potential antimitochondrial anticancer agents: design, synthesis and biological chemistry. To overcome the two major problems associated with existing anticancer drugs (resistance to therapy and lack of discrimination between normal and cancer cells) there is much current interest in targeting mitochondrial cell death pathways in chemotherapy. This project will probe the mode of action of a series of gold complexes containing pyridylphosphines that may act by an antimitochondrial mechanism. Also, we will evaluate a new family of gold complexes based on carbene rather than phosphine components. Such compounds offer the potential advantages of ease of synthesis, lower toxicity and the ability to fine-tune molecular properties to maximise anticancer activity.Read moreRead less
Simulation of ligand binding-induced conformational changes in biological systems. This project is focused on the development of a methodology that will allow using molecular dynamics simulations to study fundamental biochemical reactions. The benefits to the Australian community are two fold: i) the software developed will be made available to the whole scientific community through peer-reviewed publication. Australian researchers will have the possibility to exploit the software in advance thr ....Simulation of ligand binding-induced conformational changes in biological systems. This project is focused on the development of a methodology that will allow using molecular dynamics simulations to study fundamental biochemical reactions. The benefits to the Australian community are two fold: i) the software developed will be made available to the whole scientific community through peer-reviewed publication. Australian researchers will have the possibility to exploit the software in advance through collaborations with our research group. ii) During this collaboration Australian PhD students will have the opportunity to spend a few months overseas to learn about the most advanced computational techniques and interact with top researchers in the computational chemistry field.Read moreRead less