Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775725
Funder
Australian Research Council
Funding Amount
$465,000.00
Summary
Molecular separation and characterisation - A facility for advanced mass spectroscopy and chromatography. Characterising molecular composition is a basic need for the progress of many sciences. It is used to examine traditional and modern medicinal chemistry, bio-active peptides, molecular modulation of chemical properties, markers of disease and system status, and can also be used to elucidate molecular mechanisms and interactions in a system. This can only be achieved through precise measureme ....Molecular separation and characterisation - A facility for advanced mass spectroscopy and chromatography. Characterising molecular composition is a basic need for the progress of many sciences. It is used to examine traditional and modern medicinal chemistry, bio-active peptides, molecular modulation of chemical properties, markers of disease and system status, and can also be used to elucidate molecular mechanisms and interactions in a system. This can only be achieved through precise measurement using the frontier technologies described in this grant. This proposal ensures international competitiveness on a broad front, and supports highest level research training and bio/chemical/medical research in several priority research areas. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668543
Funder
Australian Research Council
Funding Amount
$280,000.00
Summary
A high resolution, high-throughput chromatographic system for separation and characterisation of complex samples. Purchase of this equipment will support innovative and collaborative research addressing three of the National Research Priority areas. For example, defining novel drug delivery systems, or the chemical components present in Australia's bioresources, addresses 'Frontier technologies for building and transforming Australian industries', particularly the priority goals of breakthrough ....A high resolution, high-throughput chromatographic system for separation and characterisation of complex samples. Purchase of this equipment will support innovative and collaborative research addressing three of the National Research Priority areas. For example, defining novel drug delivery systems, or the chemical components present in Australia's bioresources, addresses 'Frontier technologies for building and transforming Australian industries', particularly the priority goals of breakthrough science and frontier technologies. The research into trace components in food products, and on fruit fly chemistry, relates to National Research priority four 'Safeguarding Australia', with a priority goal of protecting Australia from invasive diseases and pests. Nutraceutical research addresses the goal of 'Promoting and maintaining good health'.Read moreRead less
Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453651
Funder
Australian Research Council
Funding Amount
$907,511.00
Summary
Small Molecule NMR Facility for Accelerated Drug Discovery. This project will accelerate the drug discovery process by establishing a world-class small-molecule Nuclear Magnetic Resonance (NMR) facility. The requested instrumentation will enable high throughput structural analysis of synthetic lead compounds, expedite natural product isolation and identification and enhance NMR-based drug screening. This facility will support both existing and new programs in Victorian universities, particularly ....Small Molecule NMR Facility for Accelerated Drug Discovery. This project will accelerate the drug discovery process by establishing a world-class small-molecule Nuclear Magnetic Resonance (NMR) facility. The requested instrumentation will enable high throughput structural analysis of synthetic lead compounds, expedite natural product isolation and identification and enhance NMR-based drug screening. This facility will support both existing and new programs in Victorian universities, particularly Medicinal and Biological Chemistry, and achieve internationally competitive research capabilities. Outcomes will include the development of new pharmaceuticals, increased local and international collaboration and the training of new scientists in state-of-the-art spectroscopic techniques for identification of natural products and synthetic molecules of pharmacological importance.
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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883096
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Analytical and Preparative Enantioselective Chromatography. Enantiomers are forms of the same molecule that are non-superimposable mirror images of one another, like a left hand and a right hand. Because they are so similar they are very difficult to separate. However, they have very different biological properties, such as when used as drugs. One enantiomer may be beneficial while the other has no effect or sometimes is even toxic. Therefore it is important to be able to tell how much of ea ....Analytical and Preparative Enantioselective Chromatography. Enantiomers are forms of the same molecule that are non-superimposable mirror images of one another, like a left hand and a right hand. Because they are so similar they are very difficult to separate. However, they have very different biological properties, such as when used as drugs. One enantiomer may be beneficial while the other has no effect or sometimes is even toxic. Therefore it is important to be able to tell how much of each enantiomer is present in a sample and to be able to separate them. This facility will allow us to do both of these things.Read moreRead less
New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides a ....New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides and proteins in drug-like molecules. This is a highly interdisciplinary project, spanning structural biology, molecular design, medicinal chemistry, molecular biology and electrophysiology, and the training of PhD graduates with such broad experience represents another national benefit of the project.Read moreRead less
Raman and synchrotron spectroscopy of nano-scale drug interactions and molecular processes in single living cells. The need for potent low-cost drugs is ever increasing, yet effective ways to screen for new drugs remain elusive. A spectroscopic approach to screening drugs in living cells would seem a logical alternative to chemically based and morphological methods that are the status quo. In this context we are developing methodology to analyse molecular target sites in single living cells for ....Raman and synchrotron spectroscopy of nano-scale drug interactions and molecular processes in single living cells. The need for potent low-cost drugs is ever increasing, yet effective ways to screen for new drugs remain elusive. A spectroscopic approach to screening drugs in living cells would seem a logical alternative to chemically based and morphological methods that are the status quo. In this context we are developing methodology to analyse molecular target sites in single living cells for two of the most devastating diseases to afflict human kind, namely malaria and cancer. New ways of rapidly screening drugs in living cells prior to clinical trials will save an enormous amount of time, money and ultimately lives.Read moreRead less
Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the st ....Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the structure of membrane proteins are difficult to determine and the newly developed techniques used for the structural determination of this membrane-associated protein will be suitable for studying other membrane proteins and receptors of pharmaceutical importance.Read moreRead less
New polymerisation processes for the synthesis of novel biopolymers. Synthetic peptide-based vaccines, formed via polymerisation of small bioactive motifs, possess several advantages over traditional approaches and promise to be the multi-disease targeting vaccines of the future. Disease targets will include influenza and hepatitis C viruses and a toxin from enteropathogenic Escherichia coli. These three diseases are in desperate need of novel vaccine approaches and the chemistries described in ....New polymerisation processes for the synthesis of novel biopolymers. Synthetic peptide-based vaccines, formed via polymerisation of small bioactive motifs, possess several advantages over traditional approaches and promise to be the multi-disease targeting vaccines of the future. Disease targets will include influenza and hepatitis C viruses and a toxin from enteropathogenic Escherichia coli. These three diseases are in desperate need of novel vaccine approaches and the chemistries described in this proposal represent a conceptual leap over traditional, and so far ineffective approaches investigated thus far. Synthetic antifreeze proteins and bioelastomers will also be constructed using our catalysis driven polymerisation process and applied to unmet medical and industrial needs.Read moreRead less
New methods for the synthesis of stable cyclic peptides. This proposal will design, synthesise and evaluate novel carbocyclic analogues of cyclic peptides which have application in the treatment of pain, diabetes management, malaria, and cancer therapy and diagnosis. The carbocyclic analogues will have improved biostability and will also provide the opportunity for oral administration. Carbacyclic analogues of insulin could lead to improved treatment of Australia's 1.2 million diabetics includi ....New methods for the synthesis of stable cyclic peptides. This proposal will design, synthesise and evaluate novel carbocyclic analogues of cyclic peptides which have application in the treatment of pain, diabetes management, malaria, and cancer therapy and diagnosis. The carbocyclic analogues will have improved biostability and will also provide the opportunity for oral administration. Carbacyclic analogues of insulin could lead to improved treatment of Australia's 1.2 million diabetics including many Aboriginal Australians who are particularly susceptible to Type II diabetes and its debilitating complications.Read moreRead less