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
Mass Spectrometric Investigations of Conformation and Dynamics of Biological Complexes. The new collaboration between the leading mass spectrometry groups at University Wollongong and Cambridge University will benefit both partners. Researchers at Wollongong will have access to an ion mobility mass spectrometry technology not currently available in Australia that will contribute to our understanding of complicated cellular processes such as chromosome replication. The researchers' experience wit ....Mass Spectrometric Investigations of Conformation and Dynamics of Biological Complexes. The new collaboration between the leading mass spectrometry groups at University Wollongong and Cambridge University will benefit both partners. Researchers at Wollongong will have access to an ion mobility mass spectrometry technology not currently available in Australia that will contribute to our understanding of complicated cellular processes such as chromosome replication. The researchers' experience with this technology will pave the way for introduction of the technology to Australia and benefit the wider scientific community in wide-ranging projects such as development of new antibiotics and vaccines. Students from both institutions will benefit from experiencing science from an international perspective.Read moreRead less
Conformationally constrained and immobilized beta-peptides. The research builds on world-class expertise in Australia (particularly Adelaide) in proteomics to provide a basis for fundamental advances in chemistry that will underpin the development of new pharmaceuticals and smart materials, and future technologies and industries. We create a mix of research at the interface of disciplines within academia and industry, with linkages to the very best international researchers and centres. A new cr ....Conformationally constrained and immobilized beta-peptides. The research builds on world-class expertise in Australia (particularly Adelaide) in proteomics to provide a basis for fundamental advances in chemistry that will underpin the development of new pharmaceuticals and smart materials, and future technologies and industries. We create a mix of research at the interface of disciplines within academia and industry, with linkages to the very best international researchers and centres. A new critical mass of expertise in a number of advancing areas of chemistry, biology, and materials science will be introduced to Australia. This will enhance existing strengths and opportunities in proteomics and biomedical research for the treatment of disease.Read moreRead less
Design and evaluation of new environmentally-benign herbicides that inhibit branched-chain amino acid biosynthesis. Herbicides interfere with processes that occur in plants, such as photosynthesis or the biosynthesis of certain amino acids. In this project we will focus on branched-chain amino acid biosynthesis, designing and evaluating inhibitors of the first two enzymes in this process. Based on their three dimensional structures we will develop an understanding of the molecular features that ....Design and evaluation of new environmentally-benign herbicides that inhibit branched-chain amino acid biosynthesis. Herbicides interfere with processes that occur in plants, such as photosynthesis or the biosynthesis of certain amino acids. In this project we will focus on branched-chain amino acid biosynthesis, designing and evaluating inhibitors of the first two enzymes in this process. Based on their three dimensional structures we will develop an understanding of the molecular features that contribute to a potent inhibitor and those that are required for it to be effective upon plants. Using this information we will design and synthesis new compounds as potential environmentally-benign herbicides.Read moreRead less
Single Molecule Studies of Replisomal Function. It has recently become possible to watch the copying of DNA molecules with a specialized microscope in real time. This process requires assembly of a complex molecular machine on the DNA, followed by triggering of its function, and yields exquisitely detailed information about how the machine works. In this new collaboration between scientists in Australia and the U.S.A., we will assemble these machines on single DNA molecules, watch how they work ....Single Molecule Studies of Replisomal Function. It has recently become possible to watch the copying of DNA molecules with a specialized microscope in real time. This process requires assembly of a complex molecular machine on the DNA, followed by triggering of its function, and yields exquisitely detailed information about how the machine works. In this new collaboration between scientists in Australia and the U.S.A., we will assemble these machines on single DNA molecules, watch how they work and simultaneously measure the very small forces that the machines generate. This will give Australian scientists access to a new technology for studying molecular machines.Read moreRead less
Joint Theoretical and Experimental Electron Momentum Spectroscopic Studies for DNA Bases. The study of DNA structure is an area of intense research activity and continues to reveal new levels of complexity and diversity. Recent experiments (Science, 2002) provided direct evidences of the adenine non-planarity, indicating non-rigidity of DNA bases. Electron momentum spectroscopy (EMS) has been identified to be an appropriate technique in the study of chemical binding mechanism and orbitals at mol ....Joint Theoretical and Experimental Electron Momentum Spectroscopic Studies for DNA Bases. The study of DNA structure is an area of intense research activity and continues to reveal new levels of complexity and diversity. Recent experiments (Science, 2002) provided direct evidences of the adenine non-planarity, indicating non-rigidity of DNA bases. Electron momentum spectroscopy (EMS) has been identified to be an appropriate technique in the study of chemical binding mechanism and orbitals at molecular level. The aims of the project is to study orbitals and interactions of DNA and RNA bases such as adenine, thymine (uracil), guanine and cytosine using momentum space quantum mechanics and EMS experimental techniques. The outcome of the project will improve our understanding of the DNA double helical strand structure.Read moreRead less
Structural studies of mammalian dimeric dihydrodiol dehydrogenase and L-xylulose reductase. The aim of the research is determine the structures and mechanisms of mammalian dimeric dihrodiol dehydrogenase and L-xylulose reductase. Mammalian dihydrodiol dehydrogenase exists in multiple forms in mammalian tissues. The dimeric form of the enzyme has a primary structure distinct from previously known mammalian enzymes and may constitute a novel protein family with prokaryotic proteins. L-Xylulose ....Structural studies of mammalian dimeric dihydrodiol dehydrogenase and L-xylulose reductase. The aim of the research is determine the structures and mechanisms of mammalian dimeric dihrodiol dehydrogenase and L-xylulose reductase. Mammalian dihydrodiol dehydrogenase exists in multiple forms in mammalian tissues. The dimeric form of the enzyme has a primary structure distinct from previously known mammalian enzymes and may constitute a novel protein family with prokaryotic proteins. L-Xylulose reductase is an enzyme of the uronate cycle that accounts for about 5% of the total glucose metabolism per day in humans. We propose to determine the first structure of a L-xylulose reductase.Read moreRead less
Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesi ....Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesis of inhibitors of these enzymes.Read moreRead less
New clean and green aqueous metathesis. The technique of olefin metathesis has already yielded new pharmaceuticals and materials for use in consumer products and ballistic protection. This project will help move metathesis into the realms of natures aqueous environment, a key advance if metathesis is to reveal its full potential in biological, polymeric, and pharmaceutical applications. We specifically aim to target treatments for cataract (and other conditions associated with an aging populatio ....New clean and green aqueous metathesis. The technique of olefin metathesis has already yielded new pharmaceuticals and materials for use in consumer products and ballistic protection. This project will help move metathesis into the realms of natures aqueous environment, a key advance if metathesis is to reveal its full potential in biological, polymeric, and pharmaceutical applications. We specifically aim to target treatments for cataract (and other conditions associated with an aging population) and also important new biopolymers for use in health technologies of the future.Read moreRead less
Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of ex ....Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of exposure. Structure determination of biomolecules is at the heart of identifying, diagnosing and potentially developing treatments for diseases, and thus another important reason for studying these interactions is the potential to develop new mass spectrometry based analytical methods.Read moreRead less