Praziquantel: a unique pharmaceutical challenge. Generating effective and affordable drugs for the treatment of tropical diseases is a huge public health challenge. We will pioneer an open source approach to collaborative research in drug discovery. We aim to discover an inexpensive route to an important pharmaceutical so that it can be greatly improved and distributed to the affected populations for a realistic price. Success in this project will improve the lives of millions of sufferers of th ....Praziquantel: a unique pharmaceutical challenge. Generating effective and affordable drugs for the treatment of tropical diseases is a huge public health challenge. We will pioneer an open source approach to collaborative research in drug discovery. We aim to discover an inexpensive route to an important pharmaceutical so that it can be greatly improved and distributed to the affected populations for a realistic price. Success in this project will improve the lives of millions of sufferers of this disease, and demonstrate a new way of doing research on drugs for related diseases such as malaria. Read moreRead less
Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
Total Synthesis of the Microsclerodermins: Anti-fungal Cyclic Peptides. Fungal infections are one of the major causes of morbidity and mortality in the increasing immunocompromised patient population, which includes AIDS, chemotherapy and organ transplant patients. The aim of this project is to discover new anti-fungal treatments for drug-resistant pathogenic fungal infections, based on the microsclerodermin family of natural products. The small quantity of microsclerodermin isolated from the na ....Total Synthesis of the Microsclerodermins: Anti-fungal Cyclic Peptides. Fungal infections are one of the major causes of morbidity and mortality in the increasing immunocompromised patient population, which includes AIDS, chemotherapy and organ transplant patients. The aim of this project is to discover new anti-fungal treatments for drug-resistant pathogenic fungal infections, based on the microsclerodermin family of natural products. The small quantity of microsclerodermin isolated from the natural environment hampers the development of anti-fungal agents from this natural product. Innovative synthetic methods will be developed to prepare large quantities of microsclerodermins and related compounds for biological testing, thereby furthering the development of this promising class of anti-fungal drugs.Read moreRead less
Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produce ....Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produced and may also benefit from advances in our understanding of this elusive virus resulting from the project.Read moreRead less
Raman and synchrotron spectroscopy of nano-scale drug interactions and molecular processes in single living cells. The need for potent low-cost drugs is ever increasing, yet effective ways to screen for new drugs remain elusive. A spectroscopic approach to screening drugs in living cells would seem a logical alternative to chemically based and morphological methods that are the status quo. In this context we are developing methodology to analyse molecular target sites in single living cells for ....Raman and synchrotron spectroscopy of nano-scale drug interactions and molecular processes in single living cells. The need for potent low-cost drugs is ever increasing, yet effective ways to screen for new drugs remain elusive. A spectroscopic approach to screening drugs in living cells would seem a logical alternative to chemically based and morphological methods that are the status quo. In this context we are developing methodology to analyse molecular target sites in single living cells for two of the most devastating diseases to afflict human kind, namely malaria and cancer. New ways of rapidly screening drugs in living cells prior to clinical trials will save an enormous amount of time, money and ultimately lives.Read moreRead less
New approaches to inhibition of activity of HIV integrase. This project aims to assist in the development of novel anti-HIV drugs that will benefit the 17000 Australians and more than 33 million people worldwide who are currently suffering with this terrible disease. The project will utilise state-of-the-art approaches in structure-based drug design to identify and synthesise compounds as leads for the development of anti-HIV drugs. Furthermore, the project will provide invaluable training for t ....New approaches to inhibition of activity of HIV integrase. This project aims to assist in the development of novel anti-HIV drugs that will benefit the 17000 Australians and more than 33 million people worldwide who are currently suffering with this terrible disease. The project will utilise state-of-the-art approaches in structure-based drug design to identify and synthesise compounds as leads for the development of anti-HIV drugs. Furthermore, the project will provide invaluable training for the researchers involved and enhance the relationship between the academic and commercial collaborators.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100087
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
Regional Facility for Molecular Characterisation and Mapping. Researchers at the Schools of Chemistry at The Australian National University and University of Wollongong are involved in a range of projects where new molecules are synthesised or discovered in natural products such as rainforest plants and marine organisms. Some of the molecules have already shown promise against diseases such as Alzheimer's and cardiovascular disease. In order to fully characterise these molecules, two complementa ....Regional Facility for Molecular Characterisation and Mapping. Researchers at the Schools of Chemistry at The Australian National University and University of Wollongong are involved in a range of projects where new molecules are synthesised or discovered in natural products such as rainforest plants and marine organisms. Some of the molecules have already shown promise against diseases such as Alzheimer's and cardiovascular disease. In order to fully characterise these molecules, two complementary mass spectrometers, replacing ageing instrumentation will be commissioned at each site. In addition, researchers in Wollongong will acquire a MALDI mass spectrometer capable of imaging the distribution of molecules on tissues that may be pathologically important.Read moreRead less
The Design and Synthesis of Inhibitors of Human Immunodeficiency (HIV) Budding. We have a very exciting and revolutionary approach to drug design by exploiting the exquisite potent action of peptides and at the same time overcome their shortcomings as drug candidates in that they are rapidly degraded in the body. We do this by slightly modifying their chemical structure but at the same time maintaining their biological activity. We will apply this new approach to a novel protein target to inhibi ....The Design and Synthesis of Inhibitors of Human Immunodeficiency (HIV) Budding. We have a very exciting and revolutionary approach to drug design by exploiting the exquisite potent action of peptides and at the same time overcome their shortcomings as drug candidates in that they are rapidly degraded in the body. We do this by slightly modifying their chemical structure but at the same time maintaining their biological activity. We will apply this new approach to a novel protein target to inhibit one of the main steps in the budding of Human Immunodeficiency (HIV) from infected cells. This unique combination of novel chemistry and drug design target makes this project highly innovative and with enormous potential to accelerate the identification of new drugs for HIV treatment.Read moreRead less
The Development of Computer-Aided Molecular Modelling and Drug Design Techniques for Flexible Enzyme Targets - New Anti-HIV Agents. The dynamic motion of proteins upon binding of small molecules is crucial in many cases for the function of the protein or for the function of drugs acting upon the protein. Current methods in computer-aided design of small molecules binding to proteins do not take this protein flexibility fully into account. This project intends to develop molecular dynamics simula ....The Development of Computer-Aided Molecular Modelling and Drug Design Techniques for Flexible Enzyme Targets - New Anti-HIV Agents. The dynamic motion of proteins upon binding of small molecules is crucial in many cases for the function of the protein or for the function of drugs acting upon the protein. Current methods in computer-aided design of small molecules binding to proteins do not take this protein flexibility fully into account. This project intends to develop molecular dynamics simulation techniques for this purpose, initially using the HIV reverse transcriptase enzyme as the target protein. The methods developed will, however, be universally applicable. The project further aims to design, synthesise and test novel medicinal agents specifically against drug resistance in HIV.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.Read moreRead less