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.
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.
Rational design of new drug candidates for the treatment of Trypanosoma cruzi infection. There is a serious shortage of safe and effective drugs to treat Chagas disease which is caused by a parasitic infection. This project aims to design and identify new drug candidates by defining the disposition profile within the body which is necessary to achieve a therapeutic effect.
Translating pharmacokinetic and pharmacodynamic data to better design new drugs for the treatment of Trypanosoma cruzi infection. New drugs to treat T. cruzi infection are urgently needed, however their design has been hampered by an incomplete understanding of complex host-parasite interactions, inadequate in vitro and in vivo tools to rigorously define activity during drug discovery, and a poor appreciation of concentration/effect relationships. This project aims to develop new and much needed ....Translating pharmacokinetic and pharmacodynamic data to better design new drugs for the treatment of Trypanosoma cruzi infection. New drugs to treat T. cruzi infection are urgently needed, however their design has been hampered by an incomplete understanding of complex host-parasite interactions, inadequate in vitro and in vivo tools to rigorously define activity during drug discovery, and a poor appreciation of concentration/effect relationships. This project aims to develop new and much needed in vitro methods to better define the kinetic and dynamic activity of new drug candidates, and will provide a rational basis for translating this information into lengthy animal models of T. cruzi infection. The outcome aims to be rationally designed drug candidates that are available in a shorter period of time and are suitable for further development.Read moreRead less
Structure-based design of inhibitors of HIV-1 integrase. This project will produce compounds that block human immunodeficiency virus (HIV) replication. These compounds will benefit the 17000 Australians and more than 34 million people worldwide who are currently suffering with this terrible disease.
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
Multifunctional biodegradable nanoparticles for enhanced DNA vaccine delivery. DNA vaccine, which shows better immunological and economic merits than conventional vaccines, suffers clinical failure due to the difficulty of delivering intact DNA molecules to relevant cells. This project seeks to develop smart polymer nanospheres to protect the DNA molecules from premature degradation in order to improve its efficacy.