Fragment based screening to deliver drugs targeting tuberculosis and the gametocyte and liver stages of Plasmodium. This project will identify natural products that bind to critical proteins in malaria and tuberculosis to discover new ways to treat these diseases.
Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysica ....Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysical binding assays to characterise compounds that are produced on small scale using parallel chemistry. This approach will enable better chemical probes to be developed more rapidly at lower cost than is currently possible.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100071
Funder
Australian Research Council
Funding Amount
$290,000.00
Summary
Chemi–biology computational platform for lead discovery in infectious disease. A challenge in fighting infectious disease is in finding new bioactive compounds. This facility will provide a high performance computational environment designed to accelerate the discovery of quality compounds for use in anti-infective medicine.
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100226
Funder
Australian Research Council
Funding Amount
$424,000.00
Summary
Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not curren ....Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not currently available in Australia, and help Australian researchers remain internationally competitive in breakthrough science and frontier technologies. The research enabled by this facility will lead to development of new drug candidates by the emerging Australian biotechnology industry.Read moreRead less