Engineered Hydroxamic Acids for Zirconium-89 Positron Emission Tomography (PET) Imaging of Prostate Cancer. Positron emission tomography (PET) using a zirconium-89-ligand complex bound to a prostate-specific membrane antigen is used to detect and monitor prostate cancer. The hydroxamic acid-based ligand bound to zirconium has a high affinity towards iron, which can cause metal exchange in vivo and loss of radiotracer. The project will prepare new ligands with a higher specificity towards zirconi ....Engineered Hydroxamic Acids for Zirconium-89 Positron Emission Tomography (PET) Imaging of Prostate Cancer. Positron emission tomography (PET) using a zirconium-89-ligand complex bound to a prostate-specific membrane antigen is used to detect and monitor prostate cancer. The hydroxamic acid-based ligand bound to zirconium has a high affinity towards iron, which can cause metal exchange in vivo and loss of radiotracer. The project will prepare new ligands with a higher specificity towards zirconium over iron, and measure immuno-PET imaging activity. A second series of macrocyclic zirconium-specific ligands will be prepared to establish the relationship between variable water-lipid solubility and pharmacokinetic properties. The results will increase the capability of immuno-PET for prostate cancer detection and improve survival outcomes.Read moreRead less
Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorin ....Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorinated or deuterated building blocks. The intended outcomes are to deliver advances in methods for generating structurally diverse pools of natural products, new label-free probes, knowledge of natural product biosynthesis, and excellence in training research students in frontier methods in chemical biology and drug discovery.Read moreRead less
The effect of Pt binding to CTR1 on Cu homeostasis and cell phenotype. The copper transport protein CTR1 is commonly believed to transport active cisplatin (a platinum-based anticancer agent) into the cell, but this model is inconsistent with the chemical properties of platinum (Pt) and CTR1. The project aims to interrogate the interaction between CTR1 and Pt in cells by developing new chemical tools for the study of Pt species within cells. It will then study the effect of the CTR1-Pt interacti ....The effect of Pt binding to CTR1 on Cu homeostasis and cell phenotype. The copper transport protein CTR1 is commonly believed to transport active cisplatin (a platinum-based anticancer agent) into the cell, but this model is inconsistent with the chemical properties of platinum (Pt) and CTR1. The project aims to interrogate the interaction between CTR1 and Pt in cells by developing new chemical tools for the study of Pt species within cells. It will then study the effect of the CTR1-Pt interaction on copper homeostasis and cell phenotype. It is expected that the results will provide valuable information on the status of CTR1 and Pt following interaction, and reveal whether less toxic complexes are just as effective in decreasing cell malignancy as cisplatin itself.Read moreRead less
Fluorescent sensing of the intracellular redox environment. This project aims to develop chemical approaches to measure the redox environment of living cells. Oxidation and reduction (redox) reactions are crucial for cellular health and disease and the redox status of cells is known to affect their response to external stress, but surprisingly there remains no way of efficiently and accurately determining cellular redox environments. In this project, new fluorescent redox sensors will be designe ....Fluorescent sensing of the intracellular redox environment. This project aims to develop chemical approaches to measure the redox environment of living cells. Oxidation and reduction (redox) reactions are crucial for cellular health and disease and the redox status of cells is known to affect their response to external stress, but surprisingly there remains no way of efficiently and accurately determining cellular redox environments. In this project, new fluorescent redox sensors will be designed and incorporated into assays that enable high-throughput analysis of cell types. These fundamental chemical and biochemical studies could provide the basis of future research into how redox environment can be used as a predictor for disease and therapeutic outcomes.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130101650
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Rational design of novel metal-based chaperones for tumour-selective drug delivery. This work aims to develop new drug delivery systems based on transition metal complexes for selective delivery and release of a drug in the tumour.
Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as l ....Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as least as effective as current drugs. This project will combine recent developments in stabilisation and cellular trapping of platinum(IV) pro-drugs with a range of strategies designed to limit activation of these pro-drugs to the tumour environment.Read moreRead less
Antimicrobial and anti-Leishmanial bismuth compounds and materials. The project aims to develop the bioinorganic and medicinal chemistry of bismuth and related metals to address two global health issues: parasitic infections (principally Leishmaniasis) and antibacterial resistance. Through targeting serious microbial infections, the project will research the chemical, physical, structural and biological properties of bismuth and related metals. The project will form bio-protective materials and ....Antimicrobial and anti-Leishmanial bismuth compounds and materials. The project aims to develop the bioinorganic and medicinal chemistry of bismuth and related metals to address two global health issues: parasitic infections (principally Leishmaniasis) and antibacterial resistance. Through targeting serious microbial infections, the project will research the chemical, physical, structural and biological properties of bismuth and related metals. The project will form bio-protective materials and surfaces through incorporating bismuth and its compounds into polymer matrices. It will establish the complexes’ chemical biology and toxicology through scrutinising cellular mechanisms, particularly modern metallomic techniques. New compounds developed may address the urgent and significant health issue of antibiotic resistance and help address poorly treated parasitic infections.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102687
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Development of sensors for biological redox state. The plethora of antioxidant supplements on the market to prevent aging and disease highlights the great importance of oxidation state in the body. This project involves the development of chemical compounds that can be used to measure oxidation state in living tissue by Magnetic Resonance Imaging (MRI) or microscopy and help us understand various diseases.
Development of prodrug strategies for achieving increased penetration and selective activation in solid tumours. A primary cause of cancer deaths is relapse following treatment resulting from the drug failing to penetrate and destroy all parts of the tumour. The project aims to develop anticancer agents that are better able to reach all parts of the tumour and have toxicities low enough to enable sufficient doses to be used to kill all cancer cells.
Metals in biocatalysis. Metals and enzymes are essential for the chemistry of life. This project will aim to garner the potential of metal-dependent enzymes to develop new drugs against osteoporosis, combat the spread of antibiotics resistance and optimise some of these enzymes to detoxify pesticide-polluted environments, thus contributing to global health and food security.