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
Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus. The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folde ....Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus. The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folded structure by NMR, and assayed for enzymatic activity. It can be expected that significant new insights into the molecular basis of the properties of the HIV-1 PR will be obtained. This will be an important contribution to biomedical research.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
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.
Intravital super-resolution imaging via Stimulated Emission Depletion microscopy (STED)-microendoscopy. We will develop a new technology to enable the imaging of sub-cellular structures within a biological specimen, with super-resolution. This intravital super-resolution imaging technology will build off world leading techniques to image objects with super-resolution and to perform this within a specimen, with minimal invasion. The broad ramifications of this technology apply to biology, medical ....Intravital super-resolution imaging via Stimulated Emission Depletion microscopy (STED)-microendoscopy. We will develop a new technology to enable the imaging of sub-cellular structures within a biological specimen, with super-resolution. This intravital super-resolution imaging technology will build off world leading techniques to image objects with super-resolution and to perform this within a specimen, with minimal invasion. The broad ramifications of this technology apply to biology, medical science, imaging and sensing. Important applications include the early detection of debilitating diseases and the advancement of understanding of cellular biology. This research will raise Australia's profile as a world leader in science and technology, building on our emerging presence in the biophysical sciences.Read moreRead less
A new G-protein coupled receptor target for conotoxins. We aim to understand the interaction between venom components from the marine cone snail, a major source of potential drug leads, and a key receptor in nerve cell signalling. This receptor plays a role in many nervous system functions and has been proposed as a target for treating a range of diseases including pain, depression and drug addiction. It is critical that we understand this interaction so we can fully exploit the potential of the ....A new G-protein coupled receptor target for conotoxins. We aim to understand the interaction between venom components from the marine cone snail, a major source of potential drug leads, and a key receptor in nerve cell signalling. This receptor plays a role in many nervous system functions and has been proposed as a target for treating a range of diseases including pain, depression and drug addiction. It is critical that we understand this interaction so we can fully exploit the potential of these molecules as drug leads. The potential exists for multibillion dollar markets for these new drugs that could provide significant economic benefits to Australia.Read moreRead less
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to prod ....Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to produce lead-like compounds that inhibit the protein's function and may provide novel drug candidates for further development. Furthermore the role of human host cell-associated carbohydrates in parainfluenza infection will be better understood.Read moreRead less
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produc ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced in this study will be evaluated for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cel ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced will be assayed for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less