Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this pro ....Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this project will deliver natural and new compounds for analysis of anti-cancer activity. The rewards of the development of new synthetic methods are enormous for the community and in the education of our scientists.Read moreRead less
Exploitation of unusual patterns of reactivity of peptides towards radicals. Life depends on free radical reactions of peptides and proteins but, for these compounds to exist, these must be inherently resistant to radicals. This project aims to combine state-of-the-art experiment and theoretical computations to build a detailed picture of peptide and protein radical reactivity, in order to explain this paradox and resolve ambiguities regarding processes through which radical damage to peptides o ....Exploitation of unusual patterns of reactivity of peptides towards radicals. Life depends on free radical reactions of peptides and proteins but, for these compounds to exist, these must be inherently resistant to radicals. This project aims to combine state-of-the-art experiment and theoretical computations to build a detailed picture of peptide and protein radical reactivity, in order to explain this paradox and resolve ambiguities regarding processes through which radical damage to peptides occurs and is repaired. The project also aims to critically evaluate the basic concept of the fidelity of amino acid incorporation during protein biosynthesis. The results of this project could underpin the development of new strategies and therapeutics to treat human diseases, and new materials and synthetic methods to increase the utility of peptides in biotechnology.Read moreRead less
Taking nature's lead in the development of new and improved enzyme inhibitors. This project will address some key fundamental issues associated with advancing a chemical entity from proof of principle through to a new pharmaceutical. The compounds in the study target cancer, cataract and other diseases that are confronting Australia's ageing population.
Generation of Novel Fermentation Products and their Exploitation in the Synthesis of Biologically Active Organic Compounds with Therapeutic Potential. Collections of new micro-organisms and their metabolites suitable for use in the chemical synthesis programs will emerge from the proposed research. This will provide a potentially highly-valuable national resource that could serve the needs of many laboratories around Australia by allowing them to establish more direct routes to target molecules ....Generation of Novel Fermentation Products and their Exploitation in the Synthesis of Biologically Active Organic Compounds with Therapeutic Potential. Collections of new micro-organisms and their metabolites suitable for use in the chemical synthesis programs will emerge from the proposed research. This will provide a potentially highly-valuable national resource that could serve the needs of many laboratories around Australia by allowing them to establish more direct routes to target molecules being sought in the development of new therapeutic agents and/or materials. The combined application of molecular biological, microbiological and chemical synthesis techniques in a concerted manner in the one location will lead to a raft of new opportunities for the biotech and pharmaceutical industries in Australia.Read moreRead less
Solid-phase synthesis of sulfopeptides for evaluation of chemokine-receptor recognition. This research program will develop new chemical methods for preparing biologically active molecules that contain sulphate. These molecules have important functions in controlling blood clotting, hormone activity, immune responses, and AIDS or malarial infection. The new chemical methods will be used to study the interactions of two groups of proteins that control the movement of white blood cells in inflamma ....Solid-phase synthesis of sulfopeptides for evaluation of chemokine-receptor recognition. This research program will develop new chemical methods for preparing biologically active molecules that contain sulphate. These molecules have important functions in controlling blood clotting, hormone activity, immune responses, and AIDS or malarial infection. The new chemical methods will be used to study the interactions of two groups of proteins that control the movement of white blood cells in inflammatory responses. The research will provide insights into the biochemistry of inflammation and will contribute to the development of new therapies for diseases affecting young Australians (allergy, asthma, and viral infections) as well as the elderly (atherosclerosis and arthritis).Read moreRead less
Enhanced Synthetic Efficiency For Molecular Complexity and Diversity. This project aims to introduce new, broad-spectrum strategies that permit more efficient and selective ways to access complex organic molecules. The approach involves maximising the molecule-building potential of some of the smallest accessible molecular building blocks. Significant outcomes expected from this work include much shorter chemical syntheses of important organic substances and much improved, broad scope synthetic ....Enhanced Synthetic Efficiency For Molecular Complexity and Diversity. This project aims to introduce new, broad-spectrum strategies that permit more efficient and selective ways to access complex organic molecules. The approach involves maximising the molecule-building potential of some of the smallest accessible molecular building blocks. Significant outcomes expected from this work include much shorter chemical syntheses of important organic substances and much improved, broad scope synthetic methods. The concepts introduced by this work aims to benefit industry and manufacturing by introducing more efficient methods for fine chemical manufacture, while simultaneously lowering energy use and producing less waste.Read moreRead less
Development of microflow photochemistry and its application in the synthesis of platform chemicals of pharmaceutical interest. Light induces chemical changes with a 'flick of a switch'. Following the motto 'only as small as is necessary', the project will develop a new technology for conducting photoreactions in microspace. These microdevices will be used to construct a range of related compounds or to produce a bulk amount of a specific target molecule of pharmaceutical interest.
Development and application of new peptide ligation methods for the synthesis and structure-function studies of glycoproteins. Novel synthetic technologies will be developed in this project to facilitate the preparation of glycoproteins, which are of widespread biological and therapeutic interest. These methods will enable the preparation of pure glycoproteins for detailed biochemical and functional studies eventually leading to therapeutic and diagnostic applications.
New Horizons in Diels-Alder Chemistry. Using a unique joint experimental-computational approach, we will develop reliable ways to predict the outcome of one of the most important chemical reactions. Practical applications of these new predictive tools will be developed involving powerful new versions of the reaction. Several different classes of biologically active natural products will be prepared including molecules with antitumor and antiretroviral activities. Libraries of structurally-relate ....New Horizons in Diels-Alder Chemistry. Using a unique joint experimental-computational approach, we will develop reliable ways to predict the outcome of one of the most important chemical reactions. Practical applications of these new predictive tools will be developed involving powerful new versions of the reaction. Several different classes of biologically active natural products will be prepared including molecules with antitumor and antiretroviral activities. Libraries of structurally-related analogues of natural compounds will be synthesised for biological evaluation.Read moreRead less
New peptide ligation technology for the rapid assembly of modified proteins. The project aims to develop novel technologies to enable the synthesis of modified proteins that are of widespread biological and therapeutic interest. More than 70 per cent of all human proteins are modified with a range of functionalities after translation from the ribosome. Although these modifications are of crucial importance for biological activity, characterising the effect of a given modification on function is ....New peptide ligation technology for the rapid assembly of modified proteins. The project aims to develop novel technologies to enable the synthesis of modified proteins that are of widespread biological and therapeutic interest. More than 70 per cent of all human proteins are modified with a range of functionalities after translation from the ribosome. Although these modifications are of crucial importance for biological activity, characterising the effect of a given modification on function is difficult due to problems in obtaining the protein in pure form. The goal of this project is to develop a peptide ligation methodology to access pure modified proteins in a rapid manner through the exploitation of a new reaction recently discovered in our laboratory. The project plans to explore the scope and mechanism of the new reaction as well as its application in the total chemical synthesis and structure-function studies of important modified proteins.Read moreRead less