Study the Utility of Novel Drug Polymer Conjugates. The products likely to arise from the technology described in this proposal could have application in medical, veterinary and agricultural industries. It offers the potential to treat diseases that are at present poorly treated by enabling delivery direct to the diseased organ (e.g. eye - bacterial endophthalmitis). Completion of the project will also assist a fledgling biotech company transition to a development company with a multiple produ ....Study the Utility of Novel Drug Polymer Conjugates. The products likely to arise from the technology described in this proposal could have application in medical, veterinary and agricultural industries. It offers the potential to treat diseases that are at present poorly treated by enabling delivery direct to the diseased organ (e.g. eye - bacterial endophthalmitis). Completion of the project will also assist a fledgling biotech company transition to a development company with a multiple product portfolio, which will have a direct economic benefit to Australia both in terms of potential export earnings and as an employer highly skilled staff. The project will also provide research training and career opportunities for developing Australian based researchers.Read moreRead less
Dissecting catalysis and inhibition of a unique endo-acting mannose-processing glycosidase. Defects in the attachment of carbohydrates to proteins are a hallmark of diseases such as cancer and viral infection. This project will dissect the molecular details of the bond-making and breaking steps that occur during the synthesis of glycoproteins assisting in the development of innovative new drugs.
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
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produc ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced in this study will be evaluated for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cel ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced will be assayed for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Design, Synthesis and Biological Evaluation of Rotavirus Inhibitors. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 400,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. The ....Design, Synthesis and Biological Evaluation of Rotavirus Inhibitors. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 400,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Chemical probes for the study of a unique enzyme from Mycobacterium tuberculosis. The design and chemical synthesis of molecules that selectively inhibit pathogen-specific enzymes is a validated approach toward new therapeutic agents. Mycobacterium tuberculosis contains a unique cytochrome P450 enzyme that catalyses an unusual chemical transformation to generate the product mycocyclosin. This research project will synthesise chemical probes to study the mechanism of this enzyme and the biologica ....Chemical probes for the study of a unique enzyme from Mycobacterium tuberculosis. The design and chemical synthesis of molecules that selectively inhibit pathogen-specific enzymes is a validated approach toward new therapeutic agents. Mycobacterium tuberculosis contains a unique cytochrome P450 enzyme that catalyses an unusual chemical transformation to generate the product mycocyclosin. This research project will synthesise chemical probes to study the mechanism of this enzyme and the biological role of mycocyclosin. Selective inhibitors of the enzyme will be developed, which will provide a foundation for the exploitation of these molecules in cellular research and medicine.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130101673
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Access to biomimetic carbohydrate receptors using dynamic combinatorial chemistry. This project aims to utilise novel synthetic technology for the development of cyclic peptide libraries as novel drug leads for the treatment of Dengue virus, HIV and cancer.
Interrogating diarylquinoline toxicity with targeted organic synthesis. Bedaquiline is the only new first-line treatment with a new mechanism of action to treat TB in the last 40 years, approved by the FDA on 31 December 2012. Alarmingly, this compound, has significant toxicities. The hypothesis tested in this project is that decreasing lipophilicity and basicity in this class of compounds while retaining target affinity will decrease toxicity but retain anti-TB activity. The project aims to: sy ....Interrogating diarylquinoline toxicity with targeted organic synthesis. Bedaquiline is the only new first-line treatment with a new mechanism of action to treat TB in the last 40 years, approved by the FDA on 31 December 2012. Alarmingly, this compound, has significant toxicities. The hypothesis tested in this project is that decreasing lipophilicity and basicity in this class of compounds while retaining target affinity will decrease toxicity but retain anti-TB activity. The project aims to: synthesise novel heteroarylalkylamines distinct from bedaquiline and designed to be more polar, less basic, and metabolically more stable; and, test all successfully synthesised target compounds for mechanism-based anti-tuberculosis activity, hERG-mediated cardiotoxicity, metabolic instability, and phospholipidosis.Read moreRead less