Discovery Early Career Researcher Award - Grant ID: DE170101438
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Application of boronate ester-appended scaffolds in drug-discovery. This project aims to improve carbohydrate synthesis. Glycochemistry is an increasingly important chemical science that combines organic synthesis with biology. This project will develop methodologies that incorporate boronate ester residues onto selected carbons of monosaccharides and transform them to obtain hitherto inaccessible scaffolds for drug discovery. This strategy can be used in the controlled assembly of other biologi ....Application of boronate ester-appended scaffolds in drug-discovery. This project aims to improve carbohydrate synthesis. Glycochemistry is an increasingly important chemical science that combines organic synthesis with biology. This project will develop methodologies that incorporate boronate ester residues onto selected carbons of monosaccharides and transform them to obtain hitherto inaccessible scaffolds for drug discovery. This strategy can be used in the controlled assembly of other biologically important compounds, including azacycles, oxacycles and inositols. The methods for the controlled diversification of carbohydrates are expected to be broadly applicable to scientific endeavours ranging from glycobiology to medicine. Successful execution will provide new drug-discovery tools and ensure Australia secures a competitive position in this rapidly expanding discipline.Read moreRead less
New Protocols for the Chemical Synthesis of Biologically Relevant Systems. Enzyme- and metal-catalysed processes will be developed and exploited for the purpose of establishing concise syntheses of biologically active and otherwise inaccessible natural products and their analogues. The range of structures to be targeted is structurally diverse and these have the potential to act as agrochemicals and/or as therapeutic agents for the treatment of a range of disease states in mammals including bact ....New Protocols for the Chemical Synthesis of Biologically Relevant Systems. Enzyme- and metal-catalysed processes will be developed and exploited for the purpose of establishing concise syntheses of biologically active and otherwise inaccessible natural products and their analogues. The range of structures to be targeted is structurally diverse and these have the potential to act as agrochemicals and/or as therapeutic agents for the treatment of a range of disease states in mammals including bacterial and viral infections, neuro-degenerative conditions and impaired cognitive function. Anti-angiogenic compounds that control otherwise unregulated cellular growth may also arise from these studies. The generation of new, homochiral metabolites for use in chemoenzymatic synthesis should also emerge from this project.Read moreRead less
Harnessing strain for chemical synthesis: The cyclopropane angle. This project aims to develop new reaction pathways of cyclopropanes, the smallest and most strained monocyclic ring systems, but which are also stable and easily prepared. Cyclopropanes have unique capacities to serve as highly effective building blocks in the synthesis of a wide range of otherwise difficult to access and biologically active molecular frameworks. This project will use cyclopropanes to rapidly assemble biologically ....Harnessing strain for chemical synthesis: The cyclopropane angle. This project aims to develop new reaction pathways of cyclopropanes, the smallest and most strained monocyclic ring systems, but which are also stable and easily prepared. Cyclopropanes have unique capacities to serve as highly effective building blocks in the synthesis of a wide range of otherwise difficult to access and biologically active molecular frameworks. This project will use cyclopropanes to rapidly assemble biologically active systems, especially pharmaceutically or agrochemically valuable natural products and relevant analogues.Read moreRead less
Enabling Methodologies for the Synthesis of Biologically Active Compounds. This project seeks to establish flexible methods of chemical synthesis for creating new molecular scaffolds capable of achieving selective enzyme inhibition. The approach aims to exploit the vast and biologically-programmed structural diversity associated with natural products. Unique, small molecule organic compounds will be obtained that reveal details of the operation of key enzymes in bacterial and mammalian systems. ....Enabling Methodologies for the Synthesis of Biologically Active Compounds. This project seeks to establish flexible methods of chemical synthesis for creating new molecular scaffolds capable of achieving selective enzyme inhibition. The approach aims to exploit the vast and biologically-programmed structural diversity associated with natural products. Unique, small molecule organic compounds will be obtained that reveal details of the operation of key enzymes in bacterial and mammalian systems. Such new knowledge would allow for the design of highly selective therapeutic agents relevant to the treatment of a range of diseases including bacterial infections, diabetes and cancer. The high-end scientific training and privileged forms of matter arising from this work would provide major benefit to the biotech sector.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100213
Funder
Australian Research Council
Funding Amount
$840,000.00
Summary
Multinuclear 700 MHz Nuclear Magnetic Resonance (NMR) spectrometer for advanced molecular analysis. Nuclear Magnetic Resonance (NMR) spectroscopy is the most important analytical tool in chemistry. A new 700 MHz NMR spectrometer is to replace three outdated NMR spectrometers at the NMR Facility to enable new multinuclear experiments, while serving the analytical needs of over 20 research groups in chemical and biological research.
Tags and algorithms for studies of protein structures and interactions. This project aims to develop a new set of tools to structurally characterise protein-protein and protein-ligand interactions that are difficult or impossible to analyse by other means, facilitate tracking of proteins in biological material and identify interaction partners. The project seeks to focus on the synthesis of new unnatural amino acids and tags for site-specific protein labelling, and a range of techniques for 3D s ....Tags and algorithms for studies of protein structures and interactions. This project aims to develop a new set of tools to structurally characterise protein-protein and protein-ligand interactions that are difficult or impossible to analyse by other means, facilitate tracking of proteins in biological material and identify interaction partners. The project seeks to focus on the synthesis of new unnatural amino acids and tags for site-specific protein labelling, and a range of techniques for 3D structure analysis in solution, in particular NMR spectroscopy. New algorithms are expected to be developed for optimizing NMR spectroscopy and structure calculations from sparse data. The integrated set of tools is expected to deliver better and faster structure analysis and target characterisation to accelerate early stages of drug discovery.Read moreRead less
New methods for drug discovery by NMR spectroscopy. This project aims to advance nuclear magnetic resonance (NMR) spectroscopy methods in the field of drug discovery. It addresses a long-standing bottleneck for medicinal chemists in drug development: the rapid determination of how ligand molecules bind to proteins, where they bind and their orientation in the binding site. The methods include techniques for the attachment of NMR tags to ligands and target proteins, installation of new unnatural ....New methods for drug discovery by NMR spectroscopy. This project aims to advance nuclear magnetic resonance (NMR) spectroscopy methods in the field of drug discovery. It addresses a long-standing bottleneck for medicinal chemists in drug development: the rapid determination of how ligand molecules bind to proteins, where they bind and their orientation in the binding site. The methods include techniques for the attachment of NMR tags to ligands and target proteins, installation of new unnatural amino acids in proteins, and software for automated assignment of NMR spectra and 3D structure modelling of proteins using sparse distance restraints measured by electron paramagnetic resonance (EPR) spectroscopy. The outcome is to benefit the early stages of drug discovery in the biotech industries.Read moreRead less
Generation and exploitation of novel fermentation products in the synthesis of biologically active organic compounds with therapeutic potential. Collections of new micro-organisms and their metabolites suitable for use in the synthesis of potential therapeutic agents will be established. The combined application of molecular biological, microbiological and chemical synthesis techniques in a concerted manner in the one location will lead to major new opportunities for Australian industry.
Synthesis and Biological Evaluation of Australian Sponge Metabolites. The development of concise and flexible syntheses of Australian marine natural products and analogues of ecological/therapeutic significance will emerge. Such activities will lead to the identification and evaluation of molecular entities of value in managing marine environments and help to enhance chemical synthesis capacity in Australia.
ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the d ....ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the design of peptides and proteins for targeted scientific, agricultural, biotechnology, animal health and pharmaceutical applications. CIPPS will assemble leading researchers from diverse disciplines to create a sustainable national entity that will drive new Australian industries and train next generation researchers.Read moreRead less