Engineered extrasynaptic GABAA receptors: Towards novel analgesics. Engineered extrasynaptic GABAA receptors: Towards novel analgesics. This project intends to alleviate neuropathic pain by developing drugs and good tool molecules targeting GABA-A receptors. About 20% of Australian adults suffer from neuropathic pain. Delta-containing GABA-A receptors represent attractive and novel targets for developing non-opioid analgesics. However, no drugs or good tool molecules target these receptors. This ....Engineered extrasynaptic GABAA receptors: Towards novel analgesics. Engineered extrasynaptic GABAA receptors: Towards novel analgesics. This project intends to alleviate neuropathic pain by developing drugs and good tool molecules targeting GABA-A receptors. About 20% of Australian adults suffer from neuropathic pain. Delta-containing GABA-A receptors represent attractive and novel targets for developing non-opioid analgesics. However, no drugs or good tool molecules target these receptors. This project intends to develop the needed enabling technologies, including screening assays, tool molecules and radioligands; and perform brain slice electrophysiology to confirm activity in neuronal cells. This project is expected to benefit the research community and future rational drug-discovery endeavours for drugs that modulate delta-containing receptors.Read moreRead less
Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to imp ....Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to improve its properties and reduce potential side-effects. The outcomes of this project will be understanding of a new biological process that contributes to the development of diabetes, and the discovery and characterisation of new chemical compounds that could be developed as drugs to treat diabetes.Read moreRead less
Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is ....Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is focused on studying structural features of a range of peptides and their contributions to both activity and to resistance against degradation, with the aim to develop stabilised bioactive peptide sequences for in vivo applications, allowing the full potential of peptides as drugs to be realised.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100047
Funder
Australian Research Council
Funding Amount
$380,000.00
Summary
Distributed facility for fragment based drug discovery. Distributed facility for fragment based drug discovery:
The facility aims to provide researchers with the ability to generate small molecules that modulate therapeutically and biologically important protein targets. Fragment-based drug design (FBDD) provides a rational approach to generate such biologically active compounds. The facility is designed to allow researchers throughout Australia to access the necessary infrastructure to underta ....Distributed facility for fragment based drug discovery. Distributed facility for fragment based drug discovery:
The facility aims to provide researchers with the ability to generate small molecules that modulate therapeutically and biologically important protein targets. Fragment-based drug design (FBDD) provides a rational approach to generate such biologically active compounds. The facility is designed to allow researchers throughout Australia to access the necessary infrastructure to undertake FBDD projects against a range of biologically important targets. The facility aims to enable access to high-throughput nuclear magnetic resonance spectroscopy and surface plasmon resonance, and to generate the capacity for automation in chemical synthesis and sample preparation to expedite the development of novel bioactive molecules. The development of better approaches to hit development may benefit many researchers in Australia employing FBDD.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
Surface ligation of nanomaterials for biomedical applications . The project aims to explore the synergistic effects co-ligands for target recognition and biofouling protection in nanoparticle surface patterns to enable practical atomic scale precision engineering of efficient and biofouling resistant nanosensors. The project will fundamentally characterise interfacial interactions and dynamics of ligated nano-surfaces and biomolecules via advanced computer modelling. Outcomes should include pra ....Surface ligation of nanomaterials for biomedical applications . The project aims to explore the synergistic effects co-ligands for target recognition and biofouling protection in nanoparticle surface patterns to enable practical atomic scale precision engineering of efficient and biofouling resistant nanosensors. The project will fundamentally characterise interfacial interactions and dynamics of ligated nano-surfaces and biomolecules via advanced computer modelling. Outcomes should include practical molecular design guidelines for functional ligands and predicted optimal patterns for combining functional and antifouling ligands on gold nanomaterials for biosensing technologies. The advanced predictive modelling capabilities will facilitate future practical engineering of efficient biomedical devices.Read moreRead less
Enhanced force fields for computational drug design and materials research. This project aims to improve the atomic interaction functions used to calculate the structural, dynamic and thermodynamic properties of molecules that alter net charge or structure in different environments. Predicting the stability of alternative protonation and tautomeric states for molecules bound to therapeutic targets is a major challenge in computational drug design. It is key to identifying the therapeutically act ....Enhanced force fields for computational drug design and materials research. This project aims to improve the atomic interaction functions used to calculate the structural, dynamic and thermodynamic properties of molecules that alter net charge or structure in different environments. Predicting the stability of alternative protonation and tautomeric states for molecules bound to therapeutic targets is a major challenge in computational drug design. It is key to identifying the therapeutically active chemical species as well as understanding drug transport and off-target effects. The work will expand the utility of modelling software used by over 13,000 researchers worldwide. In addition, the improved interaction functions will also help in the understanding of a wide range of other materials at an atomic level.Read moreRead less
Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes i ....Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes it can be applied to and the mechanisms underlying this technology. The outcomes of this project will facilitate the future development of peptides for biotechnology, pharmaceutical and veterinary applications.Read moreRead less
Pushing The Boundaries Of Flow Chemistry – Towards New Anti-Viral Agents. Synthetic chemistry approaches to new drugs rely on access to robust reliable reactions. Traditionally these approaches are highly wasteful with the pharmaceutical industries producing five to a hundred kilograms of waste per kilogram of product. Total flow chemistry approaches will significantly reduce waste, allow rapid reaction sequence optimisation, and seamless scale up. In a collaborative effort spanning Australia, G ....Pushing The Boundaries Of Flow Chemistry – Towards New Anti-Viral Agents. Synthetic chemistry approaches to new drugs rely on access to robust reliable reactions. Traditionally these approaches are highly wasteful with the pharmaceutical industries producing five to a hundred kilograms of waste per kilogram of product. Total flow chemistry approaches will significantly reduce waste, allow rapid reaction sequence optimisation, and seamless scale up. In a collaborative effort spanning Australia, Germany and the USA, in an exemplar of a real world application, this project will produce benefits not only in enhanced and greener synthetic approaches, but also in the development of strategies for the identification of small molecules, the precursors to a new mode of action class of anti-viral drugs.Read moreRead less
Theoretical modelling and design of safe covalent anti-cancer drugs. Covalent drugs are a new class of drugs with outstanding potential in cancer therapy. Detailed computer modelling studies will be performed to determine how these drugs interact with an important target in cancer therapy, the epithelial growth factor receptor, and thereby aid the development of new cancer treatments.