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
Improving the function of GABA-A receptors is a key property of several classes of clinically important drugs including benzodiazepines and many anticonvulsants. However, the binding sites and molecular mechanisms of these drugs remain poorly understood. Using compounds similar to those in green tea, we will determine the molecular mechanism of these drugs. This understanding will lead to the development of better drugs for treatment of anxiety, depression, epilepsy, insomnia & schizophrenia.
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
Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nucle ....Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nuclear magnetic resonance (NMR) spectroscopy detects every molecule that has a proton and is quantitative. This project plans to develop a NMR technique to escape bio-assay guided isolation by analysing a fraction library. Biotechnology innovation is dependent on novel compounds to provide new products. Replacing ‘grind and find’ with a technique that never lies would be transformational.Read moreRead less
The Pharmacology And Toxicity Of Synthetic Cannabinoids
Funder
National Health and Medical Research Council
Funding Amount
$744,808.00
Summary
Synthetic cannabinoids (SCs) have been recently linked to many deaths and hospitalizations but there is limited data available that addresses these issues. We have identified SCs which display unprecedented cannabinoid receptor function, unusual selectivity, and SCs with high activity at cannabinoid receptors. This project will define the role of CB receptors in the actions of SCs, and provide an evidence-based rationale for treating SC overdoses.
Cryo-EM Inspired Drug Discovery To Treat Human Fungal Pathogenic Infections
Funder
National Health and Medical Research Council
Funding Amount
$987,505.00
Summary
Invasive fungal infections are a major threat to global human health. These are highly prevalent in patients whose immune system is compromised (e.g. HIV, cancer or organ transplant patients). Of growing concern is the rise of new strains of fungal infections that are resistant to at least one of the four drug families being used to treat these infections. Here, we will create new therapeutics that block the activity of an enzyme whose activity is essential for the survival of these pathogens.
This project aims to develop a novel class of drugs with the potential to overcome the stability problems previously associated with protein-based drugs. We will develop novel molecules for the treatment of cancer and cardiovascular disease. This project has the potential to lead to major economic and social benefits to Australia via royalty returns from drug sales and reduced costs for health care for patients with these diseases.
Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of co ....Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of compound libraries. Dynamic combinatorial chemistry is an innovative technology with the capacity for supporting the shift from focussed to diverse compound libraries. This application seeks funding to refine dynamic combinatorial chemistry into an effective drug discovery tool.Read moreRead less
The Inhibition Of Biotin Protein Ligase As A New Source Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$750,167.00
Summary
We have become so accustomed to treating bacterial infections with antibiotics that it is hard to imagine life without them. However, the emergence of drug-resistance is creating a global health care crisis. Recently, there has not been enough attention paid to replacing old antibiotics with new products to combat drug resistance. Our team is addressing this challenge. We have discovered a new class of antibiotic that is unlike any other drug in clinical use.
Antibiotic Conjugates: Joining Together To Fight Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$697,675.00
Summary
New strategies are urgently needed to treat the rise of infections from multidrug-resistant bacteria, with standard antibiotic therapies becoming obsolete. This project will develop multiple innovative approaches to overcome antibiotic resistance, based on a core concept of appending additional functionality to existing antibiotic scaffolds. New conjugates will be synthesized, tested for antimicrobial activity, then optimized via a validated antimicrobial development pipeline.