Targeted Cancer Chemotherapy: The Potential Of L-Nucleoside Prodrugs
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
The aim of this project to develop novel anti-cancer agents. We plan to use an unusual sugar (an L-nucleoside) that is not normally found in the body. This unusual sugar has the property of being taken up by tumour cells but not normal cells. We will use this unusual sugar to transport a toxic compound inside tumour cells so that the tumour cells are killed. In this way, we will preferentially kill tumour cells but leave normal cells unaffected. Hence we will produce an anti-cancer agent that is ....The aim of this project to develop novel anti-cancer agents. We plan to use an unusual sugar (an L-nucleoside) that is not normally found in the body. This unusual sugar has the property of being taken up by tumour cells but not normal cells. We will use this unusual sugar to transport a toxic compound inside tumour cells so that the tumour cells are killed. In this way, we will preferentially kill tumour cells but leave normal cells unaffected. Hence we will produce an anti-cancer agent that is highly effective at killing tumour cells but has few side-effects because it does not enter normal cells. Experimentally we will synthesise compounds where the L-nucleoside is attached to a toxic agent, fluorouridine or cisplatin analogues. We will then assess the ability of these novel compounds to kill tumour cells grown in the laboratory as well as tumours growing in mice. Additionally we will attempt to determine the mechanism of action of these drugs by investigating the following: the transport properties of the drugs; how and where these drugs damage DNA; the effect of the gene, p53, which can act to stop tumour growth. The ultimate aim of this project is to develop a novel class of anti-tumour agent based on L-nucleosides. These L-nucleoside analogues are expected to be more efficient at killing tumour cells but have fewer side effects.Read moreRead less
L-amino Acid Sensing By The Extracellular Calcium-sensing Receptor: Molecular, Cellular And In Vivo Studies
Funder
National Health and Medical Research Council
Funding Amount
$362,545.00
Summary
Recent work by Dr Conigrave and colleagues demonstrates for the first time that protein and calcium metabolism are linked at the molecular level by the widely distributed calcium-sensing receptor. The project will aim to demonstrate the physiological significance of this finding by testing whether L-amino acids, the building blocks of body protein, exert receptor-dependent control over the secretion and blood levels of hormones that regulate body calcium levels. It will further test the hypothes ....Recent work by Dr Conigrave and colleagues demonstrates for the first time that protein and calcium metabolism are linked at the molecular level by the widely distributed calcium-sensing receptor. The project will aim to demonstrate the physiological significance of this finding by testing whether L-amino acids, the building blocks of body protein, exert receptor-dependent control over the secretion and blood levels of hormones that regulate body calcium levels. It will further test the hypothesis by determining whether amino acids exert receptor-dependent control over the proliferation of bone forming cells and urinary excretion of calcium.Read moreRead less