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
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
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
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.
New methods for the chemical synthesis of a library of glycopeptide-based tri-component cancer vaccines. A novel method for the synthesis of tumour-associated glycopeptides will be developed in this research as well as the preparation of a library of glycopeptide-based cancer vaccines. These vaccines will be tested in immunological studies with a view to elucidating new immune-based therapies for the treatment of cancer.
Discovery Early Career Researcher Award - Grant ID: DE140101632
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Development of Innovative Chemical Tools for Studying Glycosyltransferases . This project aims to develop chemical probes capable of selectively binding and inhibiting two classes of carbohydrate processing enzymes known as O-linked beta-N-acetylglucosamine transferase and sialyltransferases. These enzymes are overexpressed in various cancers and play critical roles in cancer progression. Probes will be developed to analyse the activities of these enzymes in cancer cells.
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.
Discovery Early Career Researcher Award - Grant ID: DE120101653
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Selective fluorination chemistry: a tool for creating bioactive, shape-controlled peptides. Fluorine atoms are desirable substituents in drug candidates because they can increase metabolic stability and hydrophobicity, and because they can be used to constrain molecules into optimal bioactive conformations. These concepts are being exploited to create shape-controlled peptides with applications in anti-cancer and anti-microbial therapy.
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.
Discovery of bioactive natural substances from uncultured bacteria and their production using photosynthetic reactor technology. The range and rate of natural product discovery is the limiting factor in developing new therapies for cancer and infectious disease. This research will enable the discovery of new drugs, coupled to their production in a photosynthetic expression system. This represents a truly “green” and sustainable technology for the pharmaceutical industry.