Chemical tools for the study of mycobacterial glycolipid biosynthesis. Mycobacteria are responsible for human morbidity and mortality on a immense scale. The cell wall structure of these bacteria is extremely complex and offers many novel therapeutic opportunities. In this proposal we will use a synergetic interplay of chemistry, biochemistry and microbiology to study the biosynthesis of essential cell wall molecules conserved across all mycobacteria, the phosphatidylinositol mannosides. Substr ....Chemical tools for the study of mycobacterial glycolipid biosynthesis. Mycobacteria are responsible for human morbidity and mortality on a immense scale. The cell wall structure of these bacteria is extremely complex and offers many novel therapeutic opportunities. In this proposal we will use a synergetic interplay of chemistry, biochemistry and microbiology to study the biosynthesis of essential cell wall molecules conserved across all mycobacteria, the phosphatidylinositol mannosides. Substrates and inhibitors will be prepared and studied using novel biochemical and microbiological methods. This project will enhance our understanding of cell wall synthesis in mycobacteria and will lay the ground work for the discovery of novel antibiotics.Read moreRead less
Lipid and Carbohydrate Based Systems to Target and Deliver Peptide Drug Candidates to Specific Cells. The demand for novel effective, orally available medicines to treat a wide range of diseases (cancer, pain - ageing Australian population) is increasing exponentially. Conjugation of peptide drug or vaccine candidates with lipids and/or sugars represents an important, novel strategy in the drug delivery and targeting field. Increasing the lipophilicity improves absorption through intestinal muco ....Lipid and Carbohydrate Based Systems to Target and Deliver Peptide Drug Candidates to Specific Cells. The demand for novel effective, orally available medicines to treat a wide range of diseases (cancer, pain - ageing Australian population) is increasing exponentially. Conjugation of peptide drug or vaccine candidates with lipids and/or sugars represents an important, novel strategy in the drug delivery and targeting field. Increasing the lipophilicity improves absorption through intestinal mucosal membranes. The carbohydrates increase the compound's aqueous solubility and can utilize active transport systems and can target the site required for its biological function. There is no limit to the areas of medicine and public health that would benefit from this revolutionary new technology.Read moreRead less
Liposaccharide based peptide and vaccine delivery systems: improving the bioavailability and immunogenicity of Luteinizing Hormone-Releasing Hormone. This project aims to develop new lipid- and sugar-based drug delivery systems for Luteinizing-hormone-releasing hormone (LHRH), a hormone which regulates the level of enzymes involved in fertility conditions and prostate cancers. This technology could be extended to significantly increase the number of drugs available on the market, such as peptide ....Liposaccharide based peptide and vaccine delivery systems: improving the bioavailability and immunogenicity of Luteinizing Hormone-Releasing Hormone. This project aims to develop new lipid- and sugar-based drug delivery systems for Luteinizing-hormone-releasing hormone (LHRH), a hormone which regulates the level of enzymes involved in fertility conditions and prostate cancers. This technology could be extended to significantly increase the number of drugs available on the market, such as peptide drugs and vaccines.Read moreRead less
Development of disulphide-rich peptides for drug design. Peptides are an outstanding source of potential drug leads. This project seeks to build on earlier breakthroughs by developing stable, peptide-based drugs to combat cancer and autoimmune diseases. The peptides, derived from natural sources, are anticipated to provide drug leads that can ultimately lead to treatments for these diseases.
Understanding dendrimer pharmaceuticals: The application of parallel computing to the investigation of dendrimer structure and activity. Dendrimers or starburst polymers are an important new class of synthetic material with physical and chemical properties that lie between those of small organic molecules and traditional linear polymers. One exciting area of application is the development of new dendrimer-based pharmaceuticals. This project aims to use computer-aided molecular modelling method ....Understanding dendrimer pharmaceuticals: The application of parallel computing to the investigation of dendrimer structure and activity. Dendrimers or starburst polymers are an important new class of synthetic material with physical and chemical properties that lie between those of small organic molecules and traditional linear polymers. One exciting area of application is the development of new dendrimer-based pharmaceuticals. This project aims to use computer-aided molecular modelling methods to investigate the three dimensional structure and dynamic behaviour of dendrimers. This will assist in the design of new compounds to target diseases such as secondary cancers, asthma and viral respiratory diseases.Read moreRead less
Synthetic, Molecular and Biological Studies on Novel Marine Metabolites Isolated from Great Barrier Reef Sponges. Whilst structurally remarkable marine natural products, generated via unprecedented biosynthetic pathways, continue to be isolated from organisms found on the Barrier Reef these substances remain largely unexploited in terms of both their potent biological and ecological properties. Efficient syntheses of two classes of marine metabolites will be undertaken to allow biological, biosy ....Synthetic, Molecular and Biological Studies on Novel Marine Metabolites Isolated from Great Barrier Reef Sponges. Whilst structurally remarkable marine natural products, generated via unprecedented biosynthetic pathways, continue to be isolated from organisms found on the Barrier Reef these substances remain largely unexploited in terms of both their potent biological and ecological properties. Efficient syntheses of two classes of marine metabolites will be undertaken to allow biological, biosynthetic and ecological evaluation of advanced intermediates and final products. Such evaluations will provide new insights into the therapeutic and ecological potential as well as the origins of these natural products. New agents for the management of marine ecosystems and the treatment of oncological and other diseases should emerge.Read moreRead less
Total Synthesis and Biological Evaluation of Australian Sponge Metabolites. The development of functional syntheses of Australian natural products and certain analogues of ecological and therapeutic significance will emerge. Such activities will lead to the identification and evaluation of molecular entities of value in managing marine environments, reduce the need for removal of organisms from marine environments both within and outside of Australia as well as helping maintain and enhance chemi ....Total Synthesis and Biological Evaluation of Australian Sponge Metabolites. The development of functional syntheses of Australian natural products and certain analogues of ecological and therapeutic significance will emerge. Such activities will lead to the identification and evaluation of molecular entities of value in managing marine environments, reduce the need for removal of organisms from marine environments both within and outside of Australia as well as helping maintain and enhance chemical synthesis capacity within the country. The proposed studies could lead to the identification of related natural products produced by organisms on the Great Barrier Reef and that may display even more potent activities and/or complementary ecological roles.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453832
Funder
Australian Research Council
Funding Amount
$550,910.00
Summary
New directions in biomolecular mass spectrometry. The combined UoW/ANU mass spectrometry facility supports a range of research projects in high priority areas including proteomics, mechanisms of aging, anticancer drugs and pathogenicity. The facility has several key deficiencies: 1) the ability to study very high molecular weight biomolecular complexes, 2) the ability to study ion-molecule interactions that have implications in mechanisms of chemistry in nature, and 3) researchers at ANU lack es ....New directions in biomolecular mass spectrometry. The combined UoW/ANU mass spectrometry facility supports a range of research projects in high priority areas including proteomics, mechanisms of aging, anticancer drugs and pathogenicity. The facility has several key deficiencies: 1) the ability to study very high molecular weight biomolecular complexes, 2) the ability to study ion-molecule interactions that have implications in mechanisms of chemistry in nature, and 3) researchers at ANU lack essential walk-up access to high sensitivity protein sequence analysis (MS/MS). The placement of resources that address these deficiencies in one geographical region and collaboration between these institutions will produce a research interaction unique in Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100071
Funder
Australian Research Council
Funding Amount
$290,000.00
Summary
Chemi–biology computational platform for lead discovery in infectious disease. A challenge in fighting infectious disease is in finding new bioactive compounds. This facility will provide a high performance computational environment designed to accelerate the discovery of quality compounds for use in anti-infective medicine.