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
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
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: 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
What is in therapeutically prescribed herbal medicines? Phytochemical characterisation of steroidal saponins from two popular nutraceuticals, False Unicorn and Tribulus terrestris. Plants containing steroidal saponins have long been used as therapeutic products, but their active constituents remain poorly characterized. This project aims to identify and structurally characterize steroidal saponins from False Unicorn and Tribulus terrestris, two popular nutraceuticals which are currently marketed ....What is in therapeutically prescribed herbal medicines? Phytochemical characterisation of steroidal saponins from two popular nutraceuticals, False Unicorn and Tribulus terrestris. Plants containing steroidal saponins have long been used as therapeutic products, but their active constituents remain poorly characterized. This project aims to identify and structurally characterize steroidal saponins from False Unicorn and Tribulus terrestris, two popular nutraceuticals which are currently marketed in Australia. Existing knowledge of these saponin constituents is surprisingly incomplete and inaccurate. Full structural elucidation will enable the development of 'standardised' herbal saponin profiles for better control of product quality and will allow alternatives for the herbs to be chosen, which cannot be undertaken until this composition is known. A phytochemical survey of Australian Tribulus terrestris will determine whether this native sub-species is suitable for commercial harvest.Read moreRead less
Novel Sodium Ion Channel Modulators From Australian Cephalopods. Many Australian cephalopods (octopuses, squids, cuttlefishes and nautiluses) use potent toxins to rapidly paralyse diverse prey and defend against predators. These toxins act by the efficient blocking of ion channels critical to the transmission of nerve impulses. Knowledge of these toxins can lead to safer and better drugs for the relief of chronic pain.
Allosteric Enhancers: Leads for the Therapy of Cardiovascular Disease. Cardiovascular disease (CVD - heart, stroke and blood vessel disease) kills more people each year than cancer, AIDS and traffic accidents combined. Coronary heart disease (CHD), followed by stroke, is the largest single cause of death in Australia. Allosteric enhancers are particularly attractive drug targets for the prevention of CVD due to their ability to limit injury associated with ischaemic tissue trauma selectively ....Allosteric Enhancers: Leads for the Therapy of Cardiovascular Disease. Cardiovascular disease (CVD - heart, stroke and blood vessel disease) kills more people each year than cancer, AIDS and traffic accidents combined. Coronary heart disease (CHD), followed by stroke, is the largest single cause of death in Australia. Allosteric enhancers are particularly attractive drug targets for the prevention of CVD due to their ability to limit injury associated with ischaemic tissue trauma selectively in tissues where adenosine is elevated. Whilst the development of drugs that protect against heart attack and stroke is a difficult and long term objective, any advances toward this goal would clearly be of great benefit to the community.Read moreRead less
To gain insight into the molecular mechanisms involved in antibiotic resistance shown by Gram-negative bacteria. Bacterial infections can strike anyone and usually the body's immune system, which is designed to fight infection, defeats the invading bacteria. Sometimes however, the burden of infection proves too great, so these infections can prove fatal. For 50 years, we have relied on antibiotics to successfully treat the majority of common bacterial infections. As a result, emphasis must be pl ....To gain insight into the molecular mechanisms involved in antibiotic resistance shown by Gram-negative bacteria. Bacterial infections can strike anyone and usually the body's immune system, which is designed to fight infection, defeats the invading bacteria. Sometimes however, the burden of infection proves too great, so these infections can prove fatal. For 50 years, we have relied on antibiotics to successfully treat the majority of common bacterial infections. As a result, emphasis must be placed on the disquieting reality whilst enjoy the use of antibiotics, an inescapable cost is the development of bacterial resistance. The increasing prevalence of bacterial tolerance against beta-lactams is a problem and as a result is a most pressing health issue. Read moreRead less