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
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
Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new ....Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new therapeutics, diagnostics and applications that will benefit the Australian community, and will provide excellent training of researchers in skills required for employment in the biotechnology and pharmaceutical fields.Read moreRead less
Synthesis and Applications of Antifreeze Proteins and Glycoproteins. Many cells are damaged when they are chilled below body temperatures thus limiting shelf-life for applications. For example, storage of human blood platelets is limited to 5 days at 22 degrees. This research will produce molecules that can be used in the fields of agriculture (in vitro fertilization techniques, development of improved blood lines), aquaculture and human reproductive technologies, where ice crystal growth and fr ....Synthesis and Applications of Antifreeze Proteins and Glycoproteins. Many cells are damaged when they are chilled below body temperatures thus limiting shelf-life for applications. For example, storage of human blood platelets is limited to 5 days at 22 degrees. This research will produce molecules that can be used in the fields of agriculture (in vitro fertilization techniques, development of improved blood lines), aquaculture and human reproductive technologies, where ice crystal growth and freezing are damaging. This outcome will be achieved by the synthesis of molecules that mimic natural products that allow fish to survive in the icy Arctic and Arctic Oceans and study how they are able to protect cells and tissues from damage in these extreme environments.Read moreRead less
Smart bio-mimetic self-assembled gels for biomedical applications. Advanced materials that can be used to deliver drugs, repair scars and damaged tissue are the holy grail of regenerative medicine. Recently, a class of materials called self-assembled gels have shown enormous potential in this regard. Self-assembled gels have already demonstrated their use in drug delivery and are showing great promise in the treatment of spinal injuries. This project will create an even smarter version of these ....Smart bio-mimetic self-assembled gels for biomedical applications. Advanced materials that can be used to deliver drugs, repair scars and damaged tissue are the holy grail of regenerative medicine. Recently, a class of materials called self-assembled gels have shown enormous potential in this regard. Self-assembled gels have already demonstrated their use in drug delivery and are showing great promise in the treatment of spinal injuries. This project will create an even smarter version of these gels with biological activity, especially targeting cancer and suppressing tumour growth after surgery. Our approach will help to ensure that Australians can take a leading role in this highly exciting new area of biomedical research.Read moreRead less
Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of co ....Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of compound libraries. Dynamic combinatorial chemistry is an innovative technology with the capacity for supporting the shift from focussed to diverse compound libraries. This application seeks funding to refine dynamic combinatorial chemistry into an effective drug discovery tool.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989374
Funder
Australian Research Council
Funding Amount
$550,000.00
Summary
South Australian High-Resolution and Ion-Mobility Mass Spectrometry Facility. The analytical facility will enhance (i) fundamental research to understand the mechanisms of the reactions of charged species with neutral molecules, and (ii) the provision of structural information, including the precise atomic composition of any molecule, small or large. Research supported by this facility includes (a)nanotechnology, including supramolecular chemistry, (b) bioscience: cancer research, neurodegenera ....South Australian High-Resolution and Ion-Mobility Mass Spectrometry Facility. The analytical facility will enhance (i) fundamental research to understand the mechanisms of the reactions of charged species with neutral molecules, and (ii) the provision of structural information, including the precise atomic composition of any molecule, small or large. Research supported by this facility includes (a)nanotechnology, including supramolecular chemistry, (b) bioscience: cancer research, neurodegenerate diseases (e.g. Parkinson's disease) osteoarthritis, inflammation, cardiac diseases and synthetic approaches to anticancer and other drugs.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346895
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
A Mass Directed Molecular Resolution Laboratory. The proposed "Mass Directed Molecular Resolution Laboratory" combines an integrated suite of instrumentation housed in purpose built laboratories with technical expertise to provide an unique "one stop shop" to meet the burgeoning mass spectrometry needs of the chemical community in the Melbourne area. This truly collaborative effort will service the needs of 17 research groups with 92 PhD students and post doctoral researchers and will enhance ex ....A Mass Directed Molecular Resolution Laboratory. The proposed "Mass Directed Molecular Resolution Laboratory" combines an integrated suite of instrumentation housed in purpose built laboratories with technical expertise to provide an unique "one stop shop" to meet the burgeoning mass spectrometry needs of the chemical community in the Melbourne area. This truly collaborative effort will service the needs of 17 research groups with 92 PhD students and post doctoral researchers and will enhance existing excellence in a range of areas. Finally, the laboratory will provide opportunities to: collaborate and consult with industry; train postgraduate students in instrumentation used at the cutting edge of chemical and biochemical sciences.Read moreRead less
Nicotinic acetylcholine receptors as targets in inflammatory and neurodegenerative processes. The national/community benefits that are expected to arise from this research are economic and social in nature. The novel approach employed in this project to identify inflammatory pathways and regulation has the potential to provide information that is critical in the design of novel peptide/protein based drugs. With blockbuster protein-based drugs having sales in excess of $10 billion per annum this ....Nicotinic acetylcholine receptors as targets in inflammatory and neurodegenerative processes. The national/community benefits that are expected to arise from this research are economic and social in nature. The novel approach employed in this project to identify inflammatory pathways and regulation has the potential to provide information that is critical in the design of novel peptide/protein based drugs. With blockbuster protein-based drugs having sales in excess of $10 billion per annum this proposal has the potential for very significant economic benefits for Australia. Furthermore, novel therapeutic agents for inflammatory diseases would have social benefits for Australia by decreasing the number of individuals affected and thereby reducing the physical and emotional stress associated with inflammatory diseases. Read moreRead less
Applying the CCK framework to angiogenic-based therapeutics. The aim of this project is to graft peptides involved in angiogenesis-related disorders onto a mini-protein framework. The cyclic cystine knot (CCK) framework is a plant based protein framework that has unique structural properties that make it exceptionally stable. The significance of this project is that the framework has the potential to overcome the limitations that are generally associated with peptide-based therapeutics, includin ....Applying the CCK framework to angiogenic-based therapeutics. The aim of this project is to graft peptides involved in angiogenesis-related disorders onto a mini-protein framework. The cyclic cystine knot (CCK) framework is a plant based protein framework that has unique structural properties that make it exceptionally stable. The significance of this project is that the framework has the potential to overcome the limitations that are generally associated with peptide-based therapeutics, including poor stability and bioavailability. Vastly improved therapeutic leads may be produced from this approach.Read moreRead less