Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly whe ....Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly where they act in the brain. Read moreRead less
Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly whe ....Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly where they act in the brain. Read moreRead less
Development of Pyrrolopyrimidines as Inhibitors of ATP-Binding Proteins. This project seeks to generate analogues of natural products that have been found to be active against cancer cells and tropical parasites. The new materials produced by this project will aid in the study of biochemical processes involved in diseases such as cancer and lymphatic filariasis, thus leading the way to development of these compounds as potential treatments for such diseases.
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
CHARACTERISATION OF NOVEL BIOACTIVES FROM AUSTRALIAN HONEY WITH THERAPEUTIC POTENTIAL. Honey from specific Australian flowering plants has been identified that contain significant therapeutic properties in wound healing and other treatments. The research project proposed will identify and fully characterise the bioactive components of selected Australian honey (Medihoney) with antibiotic and growth promoting activites. These aims will be supported by high resolution mass spectrometry interfaced ....CHARACTERISATION OF NOVEL BIOACTIVES FROM AUSTRALIAN HONEY WITH THERAPEUTIC POTENTIAL. Honey from specific Australian flowering plants has been identified that contain significant therapeutic properties in wound healing and other treatments. The research project proposed will identify and fully characterise the bioactive components of selected Australian honey (Medihoney) with antibiotic and growth promoting activites. These aims will be supported by high resolution mass spectrometry interfaced with HPLC and or affinity chip surfaces, 750 MHz NMR analysis and a range of relevant bioassays on specific organisms and cell lines. These outcomes will not only enhance the value of current honey-based products but have the potential to identify new therapeutic lead molecules.Read moreRead less
The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform ....The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform for new biotech companies to be formed in Australia.Read moreRead less
Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in th ....Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in the treatment of Alzheimer's disease, cancer and viral infections.Read moreRead less
High Pressure and Fluorous Approaches to Fostriecin Libraries: New Therapeutic Opportunities. The natural product, Fostriecin, displays considerable broad-spectrum anti-cancer activity, acting via a novel mechanism. However, this activity is tempered by its considerable instability, being too unstable to be used as a therapeutic agent. Using state-of-the-art approaches we will, rapidly generate libraries of more stable and biologically active fostriecin analogues and examine their potential to b ....High Pressure and Fluorous Approaches to Fostriecin Libraries: New Therapeutic Opportunities. The natural product, Fostriecin, displays considerable broad-spectrum anti-cancer activity, acting via a novel mechanism. However, this activity is tempered by its considerable instability, being too unstable to be used as a therapeutic agent. Using state-of-the-art approaches we will, rapidly generate libraries of more stable and biologically active fostriecin analogues and examine their potential to be used anti-cancer agents. This project represents an opportunity for Australia to take a significant, innovative lead in the development of hitherto unforseen therapeutic agents.Read moreRead less
Fluorous Chemistry: New tagging agents and heterocyclic-based fluorous surfactants. Fluorous chemistry is emerging as a powerful adjunct to areas of conventional parallel and combinatorial organic syntheses, and its introduction has revolutionised separation technologies. In this project two new fluorous tagging strategies will be investigated in an effort to broaden the scope of reagents that can used in synthesis. Efforts will be directed to chiral auxiliaries and to fluorous catalyst ligands. ....Fluorous Chemistry: New tagging agents and heterocyclic-based fluorous surfactants. Fluorous chemistry is emerging as a powerful adjunct to areas of conventional parallel and combinatorial organic syntheses, and its introduction has revolutionised separation technologies. In this project two new fluorous tagging strategies will be investigated in an effort to broaden the scope of reagents that can used in synthesis. Efforts will be directed to chiral auxiliaries and to fluorous catalyst ligands. In addition, a novel class of fluorous surfactant will be investigated, for its surface properties (including its ability to self assemble) and for its utility in two specific applications, selective membrane-bound protein extraction (relevant to proteomics) and ophthalmics (biomaterials).Read moreRead less
Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to sy ....Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to synthesise sex pheromones. We propose that understanding the chemical and biochemical steps employed by the flies will allow us to design inhibitors to prevent pheromone production and thus provide a novel, species specific method for controlling fruit flies.Read moreRead less