Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nucle ....Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nuclear magnetic resonance (NMR) spectroscopy detects every molecule that has a proton and is quantitative. This project plans to develop a NMR technique to escape bio-assay guided isolation by analysing a fraction library. Biotechnology innovation is dependent on novel compounds to provide new products. Replacing ‘grind and find’ with a technique that never lies would be transformational.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
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.
Towards an influenza virus glycan interaction map (Glycointeractome). This project will use nuclear magnetic resonance (NMR) spectroscopy to map carbohydrate interaction used by the virus to cause infection and spread. This information will provide new direction in anti-influenza drug discovery.
Antibiotic resistance is a looming public health crisis. New antibiotics with new mechanisms of action are desperately needed. The long-term goal of this research is to develop new drugs that disarm bacteria to overcome the problem of antibiotic resistance.
Inhibition of membrane-bound carbonic anhydrases with small molecules as a novel approach to target a safe and effective treatment for solid tumours. Over 85 per cent of human cancers are solid tumours and the prognosis for patients with advanced solid tumours is extremely poor owing to resistance to conventional chemo- and radio- therapies. Our research will underpin the development of new, safe and effective drug treatment options for cancer patients with solid tumours.