Synthesis and Applications of Antifreeze Proteins and Glycoproteins. Many cells are damaged when they are chilled below body temperatures thus limiting shelf-life for applications. For example, storage of human blood platelets is limited to 5 days at 22 degrees. This research will produce molecules that can be used in the fields of agriculture (in vitro fertilization techniques, development of improved blood lines), aquaculture and human reproductive technologies, where ice crystal growth and fr ....Synthesis and Applications of Antifreeze Proteins and Glycoproteins. Many cells are damaged when they are chilled below body temperatures thus limiting shelf-life for applications. For example, storage of human blood platelets is limited to 5 days at 22 degrees. This research will produce molecules that can be used in the fields of agriculture (in vitro fertilization techniques, development of improved blood lines), aquaculture and human reproductive technologies, where ice crystal growth and freezing are damaging. This outcome will be achieved by the synthesis of molecules that mimic natural products that allow fish to survive in the icy Arctic and Arctic Oceans and study how they are able to protect cells and tissues from damage in these extreme environments.Read moreRead less
Development of metal probes for the selective recognition of DNA. Transition metal complexes with large aromatic ligands have recently been shown to bind DNA by intercalation. However, controversy continues over their base sequence and groove selectivity. We will synthesise a range of chiral metal complexes and screen these against combinatorial oligonucleotide libraries to determine their base sequence selectivity. The information obtained will help us design better intercalators that can be us ....Development of metal probes for the selective recognition of DNA. Transition metal complexes with large aromatic ligands have recently been shown to bind DNA by intercalation. However, controversy continues over their base sequence and groove selectivity. We will synthesise a range of chiral metal complexes and screen these against combinatorial oligonucleotide libraries to determine their base sequence selectivity. The information obtained will help us design better intercalators that can be used as sensitive molecular probes and may find application as antitumour drugs. Binding interaction between the complex and DNA will be studied by NMR spectroscopy.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346895
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
A Mass Directed Molecular Resolution Laboratory. The proposed "Mass Directed Molecular Resolution Laboratory" combines an integrated suite of instrumentation housed in purpose built laboratories with technical expertise to provide an unique "one stop shop" to meet the burgeoning mass spectrometry needs of the chemical community in the Melbourne area. This truly collaborative effort will service the needs of 17 research groups with 92 PhD students and post doctoral researchers and will enhance ex ....A Mass Directed Molecular Resolution Laboratory. The proposed "Mass Directed Molecular Resolution Laboratory" combines an integrated suite of instrumentation housed in purpose built laboratories with technical expertise to provide an unique "one stop shop" to meet the burgeoning mass spectrometry needs of the chemical community in the Melbourne area. This truly collaborative effort will service the needs of 17 research groups with 92 PhD students and post doctoral researchers and will enhance existing excellence in a range of areas. Finally, the laboratory will provide opportunities to: collaborate and consult with industry; train postgraduate students in instrumentation used at the cutting edge of chemical and biochemical sciences.Read moreRead less
Experimental Charge Density Studies of Hydrogen Bonding. Hydrogen bonds, vital to all biological systems, exhibit extreme variation in chemical properties. Experimental analysis of hydrogen bonds, independent from previous theories and hypotheses, by using an expansion of current high resolution, ultra-low temperature X-ray crystallography is now possible. This allows experimental observation of electronic and electrostatic properties of previously unstudied hydrogen bonds, including weak hydrog ....Experimental Charge Density Studies of Hydrogen Bonding. Hydrogen bonds, vital to all biological systems, exhibit extreme variation in chemical properties. Experimental analysis of hydrogen bonds, independent from previous theories and hypotheses, by using an expansion of current high resolution, ultra-low temperature X-ray crystallography is now possible. This allows experimental observation of electronic and electrostatic properties of previously unstudied hydrogen bonds, including weak hydrogen bonds and those involving metal atoms. Comparison of experimental observations with predictions from high-level theoretical calculations and finally incorporation of these parameters into a prototype force field for computational chemistry will allow better predictions to be made in a range of areas including medicinal and materials chemistry.Read moreRead less
Antifreeze Proteins and Glycoproteins. Antifreeze proteins and glycoproteins permit many species of fish to survive in sub-zero oceans without freezing. These antifreeze compounds have potential applications in the frozen food industry (eg. maintaining the texture of ice cream), medical science (eg., cryosurgery) and veterinary science (eg. storage of sperm). Commercial applications are limited by the amounts of compounds available from fish and the lack of understanding of how these proteins ....Antifreeze Proteins and Glycoproteins. Antifreeze proteins and glycoproteins permit many species of fish to survive in sub-zero oceans without freezing. These antifreeze compounds have potential applications in the frozen food industry (eg. maintaining the texture of ice cream), medical science (eg., cryosurgery) and veterinary science (eg. storage of sperm). Commercial applications are limited by the amounts of compounds available from fish and the lack of understanding of how these proteins work. This research will study how natural and synthetic antifreezes inhibit ice growth in order to allow the rational design of new antifreezes and will identify new compounds with potential commercial applications as cryoprotectants.Read moreRead less
Biologically active peptides from Australian and Russian Amphibians. Bowie's group has identified many host-defence peptides from Australian anurans, including antimicrobial and anticancer active peptides, and neuropeptides that inhibit the formation of the ubiquitous chemical messenger nitric oxide. Lebedev's group from Moscow have initiated a collaboration with us to investigate active peptides from unstudied Russian frogs and newts. Preliminary investigations show these are very different f ....Biologically active peptides from Australian and Russian Amphibians. Bowie's group has identified many host-defence peptides from Australian anurans, including antimicrobial and anticancer active peptides, and neuropeptides that inhibit the formation of the ubiquitous chemical messenger nitric oxide. Lebedev's group from Moscow have initiated a collaboration with us to investigate active peptides from unstudied Russian frogs and newts. Preliminary investigations show these are very different from those isolated from Australian anurans and some already show potential for development as pharmaceuticals.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882289
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
New generation mass spectrometers for characterisation of molecular shape and size. The ion mobility mass spectrometer (IMMS at UOW) will be the first of its kind in Australia, and together with the ion trap mass spectrometer (ITMS at ANU) will continue the tradition of this partnership in providing researchers with cutting-edge instrumentation for nationally and internationally important projects including: (i) fundamental understanding of the ways in which biomolecules recognize one another, ( ....New generation mass spectrometers for characterisation of molecular shape and size. The ion mobility mass spectrometer (IMMS at UOW) will be the first of its kind in Australia, and together with the ion trap mass spectrometer (ITMS at ANU) will continue the tradition of this partnership in providing researchers with cutting-edge instrumentation for nationally and internationally important projects including: (i) fundamental understanding of the ways in which biomolecules recognize one another, (ii) investigating the structure(s) of lipids (fats) in cardiovascular disease and cataract, (iii) developing anticancer drugs, and (iv) development of new materials.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
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
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