Study the Utility of Novel Drug Polymer Conjugates. The products likely to arise from the technology described in this proposal could have application in medical, veterinary and agricultural industries. It offers the potential to treat diseases that are at present poorly treated by enabling delivery direct to the diseased organ (e.g. eye - bacterial endophthalmitis). Completion of the project will also assist a fledgling biotech company transition to a development company with a multiple produ ....Study the Utility of Novel Drug Polymer Conjugates. The products likely to arise from the technology described in this proposal could have application in medical, veterinary and agricultural industries. It offers the potential to treat diseases that are at present poorly treated by enabling delivery direct to the diseased organ (e.g. eye - bacterial endophthalmitis). Completion of the project will also assist a fledgling biotech company transition to a development company with a multiple product portfolio, which will have a direct economic benefit to Australia both in terms of potential export earnings and as an employer highly skilled staff. The project will also provide research training and career opportunities for developing Australian based researchers.Read moreRead less
Linking chemical synthesis with protein discovery to reveal key biological pathways. The project aims to pioneer a chemical biology technology to deliver a much better understanding of key molecules that regulate diseases such as cancer. For decades phorbol esters have been prominent molecules for controlling cell switches in complex diseases but our knowledge is incomplete because of the limited natural abundance of these molecules.
Molecular probes for pancreatic cancer. Cancer has overtaken heart disease as the main cause of premature death in Australia. Currently one in two men and one in three women are diagnosed with cancer during their lifetime. Pancreatic cancer is the fourth leading cause of cancer death in Australia, and the current lack of effective therapies results in a 1 year survival of just over 10%, and a 5 year survival of less than 5%. This project aims to identify and produce new compounds with novel mech ....Molecular probes for pancreatic cancer. Cancer has overtaken heart disease as the main cause of premature death in Australia. Currently one in two men and one in three women are diagnosed with cancer during their lifetime. Pancreatic cancer is the fourth leading cause of cancer death in Australia, and the current lack of effective therapies results in a 1 year survival of just over 10%, and a 5 year survival of less than 5%. This project aims to identify and produce new compounds with novel mechanisms of action that will facilitate our understanding of pancreatic carcinogenesis and provide the basis for the development of new therapeutic strategies. Australians diagnosed with pancreatic cancer in the future may directly benefit from the results of this work.Read moreRead less
Dissecting catalysis and inhibition of a unique endo-acting mannose-processing glycosidase. Defects in the attachment of carbohydrates to proteins are a hallmark of diseases such as cancer and viral infection. This project will dissect the molecular details of the bond-making and breaking steps that occur during the synthesis of glycoproteins assisting in the development of innovative new drugs.
Electrophile induced domino reaction sequences with ion-pair chiral induction. In this project, new catalysts and procedures will be developed to improve our capacity to access and modify the structure and properties of complex molecules. These methods will be used to gain access to a number of bioactive natural products in order to better evaluate and develop their therapeutic potential.
Synthesis of the pyrrolo[2,1-c][1,4]benzodiazepines: potent DNA binders. Chemicals that bind to DNA have a long history of use as anticancer drugs. In recent times, the biotechnology revolution has greatly expanded our understanding of how these drugs work and the genetic basis of a wide range of other diseases. The aim of this project is to discover novel compounds that selectively bind to DNA. Starting from a class of naturally occurring compounds (called the pyrrolobenzodiazepines) as a templ ....Synthesis of the pyrrolo[2,1-c][1,4]benzodiazepines: potent DNA binders. Chemicals that bind to DNA have a long history of use as anticancer drugs. In recent times, the biotechnology revolution has greatly expanded our understanding of how these drugs work and the genetic basis of a wide range of other diseases. The aim of this project is to discover novel compounds that selectively bind to DNA. Starting from a class of naturally occurring compounds (called the pyrrolobenzodiazepines) as a template, it will develop powerful new methods to supply wholly new DNA interactive molecules with great potential as new drugs to treat cancer or other genetic diseases.Read moreRead less
Anti-Cancer Natural Products: Total Synthesis and Biological Evaluation of Lasonolide A and Analogues. One in three men and one in four women in Australia will be diagnosed with cancer before they reach 75. Cancer is a leading cause of death within this country with 28% of deaths each year due to this disease. Although there have been advances in the treatment of various forms of cancer there remains a pressing need for new therapies with improved potency, selectivity and reduced side effects. T ....Anti-Cancer Natural Products: Total Synthesis and Biological Evaluation of Lasonolide A and Analogues. One in three men and one in four women in Australia will be diagnosed with cancer before they reach 75. Cancer is a leading cause of death within this country with 28% of deaths each year due to this disease. Although there have been advances in the treatment of various forms of cancer there remains a pressing need for new therapies with improved potency, selectivity and reduced side effects. This project will provide new compounds of potential clinical use in the treatment of cancer, thereby aiding the large population of Australians who will be affected by this disease. Furthermore, the new advanced materials produced by this project will aid in the study of biochemical processes involved in cancer.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
Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting ....Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting of tumours while protecting healthy tissue from damage. Post-treatment skin photosensitivity will be minimised by antioxidant features integrated into the photosensitisers. The development of improved photosensitisers during this project will ultimately lead to improved treatment and new alternatives for Australian cancer sufferers.Read moreRead less
The development of a rapid diagnostic test for heparanase activity. Heparanase is an enzyme that has been implicated in a number of disease states such as cancer, arthritis, multiple sclerosis and other inflammatory diseases. Characterisation of this enzyme has been slow, due in part to the lack of a reliable direct activity assay. Using a multi-disciplinary approach, this project seeks to establish a rapid assay that will provide easy determination of heparanase activity. Furthermore, this a ....The development of a rapid diagnostic test for heparanase activity. Heparanase is an enzyme that has been implicated in a number of disease states such as cancer, arthritis, multiple sclerosis and other inflammatory diseases. Characterisation of this enzyme has been slow, due in part to the lack of a reliable direct activity assay. Using a multi-disciplinary approach, this project seeks to establish a rapid assay that will provide easy determination of heparanase activity. Furthermore, this assay could provide a useful diagnostic tool in a clinical environment that would allow for the rapid assessment of these diseases, their progression and indeed response to therapy.Read moreRead less