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
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.
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.
Downsizing proteins to equipotent small molecules that activate cells. The project aims to downsize large, expensive, naturally occurring proteins to small, cheap, synthetic organic compounds engineered to have the same functions. If the methods are generally applicable for different proteins, they could be used to create new pharmaceuticals, diagnostics, flavours, perfumes, catalysts and industrial materials.
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
Elucidating the chemical and biophysical basis for the bioactivity of cyclotides: ultra-stable proteins from plants. The national/community benefits that are expected to arise from this research are economic and social in nature. In particular, this project has the potential to increase the national capacity for the development of peptides (mini-proteins) as anti-cancer drugs. With blockbuster protein-based drugs having sales in excess of $10 billion per annum this proposal has the potential for ....Elucidating the chemical and biophysical basis for the bioactivity of cyclotides: ultra-stable proteins from plants. The national/community benefits that are expected to arise from this research are economic and social in nature. In particular, this project has the potential to increase the national capacity for the development of peptides (mini-proteins) as anti-cancer 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. As well as these economic benefits a novel therapeutic agent for cancer would have enormous social benefits for Australia by decreasing the number of individuals affected and thereby reducing the subsequent emotional and physical distress associated with cancer. Read moreRead less
Common recognition elements in protein active sites: Improving the efficiencies of drug discovery. The three key contributions of biotechnology to the pharmaceutical industry are the identification of novel therapeutic targets, the creation of libraries of chemical diversity, and the high throughput screening of the libraries against the targets to create new leads. Australian research institutes and biotechnology companies are strong in the identification of novel targets, but weaker in the oth ....Common recognition elements in protein active sites: Improving the efficiencies of drug discovery. The three key contributions of biotechnology to the pharmaceutical industry are the identification of novel therapeutic targets, the creation of libraries of chemical diversity, and the high throughput screening of the libraries against the targets to create new leads. Australian research institutes and biotechnology companies are strong in the identification of novel targets, but weaker in the other two areas. The research outlined in this proposal has the potential to lead to efficient drug discovery. Success in this project will support the Australian pharmaceutical sector, lead to job creation and will have social impact through the generation of better medicines.Read moreRead less