Allosteric Enhancers: Leads for the Therapy of Cardiovascular Disease. Cardiovascular disease (CVD - heart, stroke and blood vessel disease) kills more people each year than cancer, AIDS and traffic accidents combined. Coronary heart disease (CHD), followed by stroke, is the largest single cause of death in Australia. Allosteric enhancers are particularly attractive drug targets for the prevention of CVD due to their ability to limit injury associated with ischaemic tissue trauma selectively ....Allosteric Enhancers: Leads for the Therapy of Cardiovascular Disease. Cardiovascular disease (CVD - heart, stroke and blood vessel disease) kills more people each year than cancer, AIDS and traffic accidents combined. Coronary heart disease (CHD), followed by stroke, is the largest single cause of death in Australia. Allosteric enhancers are particularly attractive drug targets for the prevention of CVD due to their ability to limit injury associated with ischaemic tissue trauma selectively in tissues where adenosine is elevated. Whilst the development of drugs that protect against heart attack and stroke is a difficult and long term objective, any advances toward this goal would clearly be of great benefit to the community.Read moreRead less
Structure and activity of host-defence peptides from Australian anurans: anticancer agents, neuropeptides and nNOS inhibitors. We have discovered peptides that may have clinical applications. This is significant as these molecules may have one or more of the following properties. They may have anti-cancer effects; they may increase the effectiveness of the immune system by enhancing lymphocyte formation; and, they may act to reduce inflammation, stroke or cardiac conditions by controlling nitri ....Structure and activity of host-defence peptides from Australian anurans: anticancer agents, neuropeptides and nNOS inhibitors. We have discovered peptides that may have clinical applications. This is significant as these molecules may have one or more of the following properties. They may have anti-cancer effects; they may increase the effectiveness of the immune system by enhancing lymphocyte formation; and, they may act to reduce inflammation, stroke or cardiac conditions by controlling nitric oxide formation. Another national benefit is that personnel involved in this project are trained to the highest international standards in peptide chemistry/mass spectrometry/nuclear magnetic resonance: currently, there are not enough trained scientists in this area to meet demand.Read moreRead less
Biologically active peptides and proteins from anurans: the relationship between structure and activity. We have identified peptides (from glands of frogs and toads), some of which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and bioactivity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide ....Biologically active peptides and proteins from anurans: the relationship between structure and activity. We have identified peptides (from glands of frogs and toads), some of which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and bioactivity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide synthase. It would be of national benefit if any of these peptides have applied application, e.g. if we can use the sex pheromone of the cane toad to reduce its population, or if we can produce an anticancer active peptide of clinical applicability.Read moreRead less
Gas Phase Dynamics of a Biological Molecular Machine: Fundamentals, Stoichiometries and Stabilities. Over the last twenty years advanced molecular measurement techniques have enabled the characterization of individual biological molecules (proteins and DNA) within different types of cells and diseased tissues. This project uses a new technique that literally "weighs" groups of proteins and/or DNA to help us understand how such large molecules fit together and function within cells (sometimes ref ....Gas Phase Dynamics of a Biological Molecular Machine: Fundamentals, Stoichiometries and Stabilities. Over the last twenty years advanced molecular measurement techniques have enabled the characterization of individual biological molecules (proteins and DNA) within different types of cells and diseased tissues. This project uses a new technique that literally "weighs" groups of proteins and/or DNA to help us understand how such large molecules fit together and function within cells (sometimes referred to as molecular machinery). More detailed knowledge of processes such as those involved in copying DNA when new cells are produced will, in the long term, improve our understanding and treatment of conditions or diseases that result from errors in molecular machinery. Read moreRead less
A Gas Phase Study of Macromolecular Biological Complexes. Following the completion of the human genome project, increased attention has focussed on the elucidation of structure and function of biopolymers in cells. The project aims to use electrospray ionisation mass spectrometry (a rapidly developing analytical technique) to detail the processes governing the formation of macromolecular complexes (DNA-protein and DNA-metal-protein) in the gas phase. We aim to explore the relevance of gas pha ....A Gas Phase Study of Macromolecular Biological Complexes. Following the completion of the human genome project, increased attention has focussed on the elucidation of structure and function of biopolymers in cells. The project aims to use electrospray ionisation mass spectrometry (a rapidly developing analytical technique) to detail the processes governing the formation of macromolecular complexes (DNA-protein and DNA-metal-protein) in the gas phase. We aim to explore the relevance of gas phase studies of these large macromolecular complexes to interactions between biopolymers in solution and cells. Ultimately, this will aid in the development of improved therapeutics tha t act on DNA and/or DNA-binding proteins and provide new information on biological processes such as replicaton.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560751
Funder
Australian Research Council
Funding Amount
$432,474.00
Summary
Facility for the Analysis of Biomacromolecular Interactions. A facility for the analysis of biological macromolecules and their interactions with ligand molecules is required to support a large number of research projects in high priority areas including mechanisms of aging, drug development and bio/nanotechnology at three different universities. The instrumentation will (i) afford quantitative measurements of binding affinities between biological and chemical macromolecules, which are available ....Facility for the Analysis of Biomacromolecular Interactions. A facility for the analysis of biological macromolecules and their interactions with ligand molecules is required to support a large number of research projects in high priority areas including mechanisms of aging, drug development and bio/nanotechnology at three different universities. The instrumentation will (i) afford quantitative measurements of binding affinities between biological and chemical macromolecules, which are available only in small quantities, and small, drug related molecules (by microcalorimetry and dual polarization interferometry), and (ii) provide equipment necessary for sample characterization and purification prior to quantitative measurements (CD spectroscopy, and FPLC equipment).Read moreRead less
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.