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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
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
Mechanistic Studies on Biologically Active Iron Chelators. The need for orally effective drugs as alternatives to invasive treatment regimens such as subcutaneous infusion is an ongoing concern in health care. This is particularly true in people suffering iron overload. In many cases this condition is present at birth and thus the administration of vital iron chelation therapy via the oral route is a much preferred option. We have unearthed a novel series of candidates for iron chelation therapy ....Mechanistic Studies on Biologically Active Iron Chelators. The need for orally effective drugs as alternatives to invasive treatment regimens such as subcutaneous infusion is an ongoing concern in health care. This is particularly true in people suffering iron overload. In many cases this condition is present at birth and thus the administration of vital iron chelation therapy via the oral route is a much preferred option. We have unearthed a novel series of candidates for iron chelation therapy (the pyridine-2-carboxaldehyde isonicotinoyl hydrazone [PCIH] analogues) which show oral activity. These chelators undergo some interesting iron catalysed oxidation chemistry and it is vital that the mechanism of this reaction be elucidated to determine whether it will be of biological significance upon administration of these compounds as iron chelators.Read moreRead less
Spotlighting biologically active Iron (Fe) chelators within cells. Anti-cancer drugs that act in ways different from traditional chemotherapeutics offer hope in evading acquired drug resistance. Previously we have studied compounds that can enter cancer cells, bind iron and halt cellular proliferation. However, there are many sources of iron in cells and we do not know from where these iron chelators acquire their iron or how these iron complexes kill cancer cells. We will tackle this problem by ....Spotlighting biologically active Iron (Fe) chelators within cells. Anti-cancer drugs that act in ways different from traditional chemotherapeutics offer hope in evading acquired drug resistance. Previously we have studied compounds that can enter cancer cells, bind iron and halt cellular proliferation. However, there are many sources of iron in cells and we do not know from where these iron chelators acquire their iron or how these iron complexes kill cancer cells. We will tackle this problem by attaching light emitting probes to known iron chelators and mapping their location within cells with high resolution fluorescence microscopy. These experiments will spotlight the cellular location of these potential drugs bound to iron for the first time, providing crucial information on their mode of action.Read moreRead less
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelati ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelation. They have discovered and characterised new chelators that show marked anticancer activity, and act by a new mechanism that overcomes problems of resistance. In this project they will pursue a course that will lead to a greater understanding of how these compounds work with the outcome that new effective anticancer drugs may emerge.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775676
Funder
Australian Research Council
Funding Amount
$290,000.00
Summary
An X-ray Diffraction Facility for Molecular Structure Determination. Characterisation of new chemical compounds demands proof of molecular structure. Whether for the identification of a new drug candidate, a material with novel properties or in the exploration of previously unknown types of compounds, X-ray crystallography is the definitive technique for this purpose. This proposal is for an X-ray diffractometer that will significantly enhance the capabilities of all synthetic and natural produc ....An X-ray Diffraction Facility for Molecular Structure Determination. Characterisation of new chemical compounds demands proof of molecular structure. Whether for the identification of a new drug candidate, a material with novel properties or in the exploration of previously unknown types of compounds, X-ray crystallography is the definitive technique for this purpose. This proposal is for an X-ray diffractometer that will significantly enhance the capabilities of all synthetic and natural products chemistry research programs undertaken at the Universities of Queensland and Newcastle, all currently in receipt of ARC funding. This research is aligned with the ARC National Research Priorities, of Promoting and Maintaining Good Health and Frontier Technologies for Building and Transforming Australian Industries.Read moreRead less
Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorin ....Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorinated or deuterated building blocks. The intended outcomes are to deliver advances in methods for generating structurally diverse pools of natural products, new label-free probes, knowledge of natural product biosynthesis, and excellence in training research students in frontier methods in chemical biology and drug discovery.Read moreRead less
Electrochemically Driven Molybdoenzyme Catalysis. Enzymes that catalyse oxidation and reduction reactions need to exchange electrons with their substrate and this supply of electrons needs to be sustained. Artificially reconstituted systems can be developed where the enzyme is coupled with an electrode and the current (electrons) exchanged during the reaction are measured directly. In this project we will reveal whether some unusual and unexplained electrochemical phenomena seen before are relat ....Electrochemically Driven Molybdoenzyme Catalysis. Enzymes that catalyse oxidation and reduction reactions need to exchange electrons with their substrate and this supply of electrons needs to be sustained. Artificially reconstituted systems can be developed where the enzyme is coupled with an electrode and the current (electrons) exchanged during the reaction are measured directly. In this project we will reveal whether some unusual and unexplained electrochemical phenomena seen before are related to the properties of the enzymes themselves or the ways in which their experiments have been conducted.Read moreRead less
Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has ....Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has potential application in biosensors and biocatalysis.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