New methods for drug discovery by NMR spectroscopy. This project aims to advance nuclear magnetic resonance (NMR) spectroscopy methods in the field of drug discovery. It addresses a long-standing bottleneck for medicinal chemists in drug development: the rapid determination of how ligand molecules bind to proteins, where they bind and their orientation in the binding site. The methods include techniques for the attachment of NMR tags to ligands and target proteins, installation of new unnatural ....New methods for drug discovery by NMR spectroscopy. This project aims to advance nuclear magnetic resonance (NMR) spectroscopy methods in the field of drug discovery. It addresses a long-standing bottleneck for medicinal chemists in drug development: the rapid determination of how ligand molecules bind to proteins, where they bind and their orientation in the binding site. The methods include techniques for the attachment of NMR tags to ligands and target proteins, installation of new unnatural amino acids in proteins, and software for automated assignment of NMR spectra and 3D structure modelling of proteins using sparse distance restraints measured by electron paramagnetic resonance (EPR) spectroscopy. The outcome is to benefit the early stages of drug discovery in the biotech industries.Read moreRead less
Tags and algorithms for studies of protein structures and interactions. This project aims to develop a new set of tools to structurally characterise protein-protein and protein-ligand interactions that are difficult or impossible to analyse by other means, facilitate tracking of proteins in biological material and identify interaction partners. The project seeks to focus on the synthesis of new unnatural amino acids and tags for site-specific protein labelling, and a range of techniques for 3D s ....Tags and algorithms for studies of protein structures and interactions. This project aims to develop a new set of tools to structurally characterise protein-protein and protein-ligand interactions that are difficult or impossible to analyse by other means, facilitate tracking of proteins in biological material and identify interaction partners. The project seeks to focus on the synthesis of new unnatural amino acids and tags for site-specific protein labelling, and a range of techniques for 3D structure analysis in solution, in particular NMR spectroscopy. New algorithms are expected to be developed for optimizing NMR spectroscopy and structure calculations from sparse data. The integrated set of tools is expected to deliver better and faster structure analysis and target characterisation to accelerate early stages of drug discovery.Read moreRead less
Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in s ....Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in solution with atomic detail. This knowledge can significantly accelerate drug development. It is otherwise only available from crystal structures that can not always be determined.Read moreRead less
A new chemotherapeutic target from Leishmania SPP. Understanding and inhibiting CYP61LD, a sterol C22 desaturase. Leishamniasis is a debilitating and often fatal disease that is caused by a parasite, Leishmania sp., which is increasing its range to include Australia. This project aims to explore possible chemotherapeutics for the disease which inhibit a particular and unique enzyme the organism uses to synthesise the sterols it requires to live.
The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform ....The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform for new biotech companies to be formed in Australia.Read moreRead less