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: 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
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Design, Synthesis and Biological Evaluation of Rotavirus Inhibitors. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 400,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. The ....Design, Synthesis and Biological Evaluation of Rotavirus Inhibitors. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 400,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.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
Novel strategies in the design and development of antivirals against dengue virus. Globally, there are 50-100 million cases of dengue fever, with 500,000 cases of the more severe dengue haemorrhagic fever, each year. Australia has between 100 and 900 cases of dengue infection annually, often from travellers, but disease outbreaks occur in northern Australia. Effective anti-viral treatment will reduce disease burden. The project contributes to an evidence-based drug design program in collaboratio ....Novel strategies in the design and development of antivirals against dengue virus. Globally, there are 50-100 million cases of dengue fever, with 500,000 cases of the more severe dengue haemorrhagic fever, each year. Australia has between 100 and 900 cases of dengue infection annually, often from travellers, but disease outbreaks occur in northern Australia. Effective anti-viral treatment will reduce disease burden. The project contributes to an evidence-based drug design program in collaboration with Australia's leading biotechnology industries. As a biotechnology industry project developing treatments for an emerging disease, it contributes to the national research priorities of Frontier technologies for building and transforming Australian industries, Promoting and maintaining good health and Safeguarding Australia.Read moreRead less
Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to prod ....Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to produce lead-like compounds that inhibit the protein's function and may provide novel drug candidates for further development. Furthermore the role of human host cell-associated carbohydrates in parainfluenza infection will be better understood.Read moreRead less
Mannosyl transfer processes in leishmania and mycobacteria. The human diseases leishmaniasis and tuberculosis are caused by infectious microorganisms. We will target pathways to the biosynthesis and degradation of parasite-specific mannose containing metabolites that play essential roles in the ability of these pathogens to cause disease. We will develop new ways to study these pathways, and will synthesize novel substrates and inhibitors that will allow the development of antituberculosis and a ....Mannosyl transfer processes in leishmania and mycobacteria. The human diseases leishmaniasis and tuberculosis are caused by infectious microorganisms. We will target pathways to the biosynthesis and degradation of parasite-specific mannose containing metabolites that play essential roles in the ability of these pathogens to cause disease. We will develop new ways to study these pathways, and will synthesize novel substrates and inhibitors that will allow the development of antituberculosis and antileishmanial drugs. This project will contribute to our national competitiveness in the newly emerging area of chemical biology.Read moreRead less
Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesi ....Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesis of inhibitors of these enzymes.Read moreRead less