An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produc ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced in this study will be evaluated for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cel ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced will be assayed for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
New polymerisation processes for the synthesis of novel biopolymers. Synthetic peptide-based vaccines, formed via polymerisation of small bioactive motifs, possess several advantages over traditional approaches and promise to be the multi-disease targeting vaccines of the future. Disease targets will include influenza and hepatitis C viruses and a toxin from enteropathogenic Escherichia coli. These three diseases are in desperate need of novel vaccine approaches and the chemistries described in ....New polymerisation processes for the synthesis of novel biopolymers. Synthetic peptide-based vaccines, formed via polymerisation of small bioactive motifs, possess several advantages over traditional approaches and promise to be the multi-disease targeting vaccines of the future. Disease targets will include influenza and hepatitis C viruses and a toxin from enteropathogenic Escherichia coli. These three diseases are in desperate need of novel vaccine approaches and the chemistries described in this proposal represent a conceptual leap over traditional, and so far ineffective approaches investigated thus far. Synthetic antifreeze proteins and bioelastomers will also be constructed using our catalysis driven polymerisation process and applied to unmet medical and industrial needs.Read moreRead less
New methods for the synthesis of stable cyclic peptides. This proposal will design, synthesise and evaluate novel carbocyclic analogues of cyclic peptides which have application in the treatment of pain, diabetes management, malaria, and cancer therapy and diagnosis. The carbocyclic analogues will have improved biostability and will also provide the opportunity for oral administration. Carbacyclic analogues of insulin could lead to improved treatment of Australia's 1.2 million diabetics includi ....New methods for the synthesis of stable cyclic peptides. This proposal will design, synthesise and evaluate novel carbocyclic analogues of cyclic peptides which have application in the treatment of pain, diabetes management, malaria, and cancer therapy and diagnosis. The carbocyclic analogues will have improved biostability and will also provide the opportunity for oral administration. Carbacyclic analogues of insulin could lead to improved treatment of Australia's 1.2 million diabetics including many Aboriginal Australians who are particularly susceptible to Type II diabetes and its debilitating complications.Read moreRead less
Development of a Diversity-Oriented Synthesis Platform. Genomic, proteomic and other studies of the molecular basis of disease are providing a constant stream of biomolecular targets for drug discovery. Identifying suitable drugs candidates to affect these targets centres around procuring a suitable library of compounds for screening. This application addresses some of the key issues related to the development of appropriate compound libraries for such screening programs.
Formation, structure and chemistry of non-covalent complexes of biomolecules via mass spectrometry. The studies proposed address fundamental issues which are essential to developments in biotechnology and related industries and of implication for human health and disease, with special attention to mechanisms of Deoxyribonucleic acid (DNA) damage, for example through Ultraviolet (UV) A and B. This has a special resonance for our sunburnt nation. The work, using world class Australian Research Cou ....Formation, structure and chemistry of non-covalent complexes of biomolecules via mass spectrometry. The studies proposed address fundamental issues which are essential to developments in biotechnology and related industries and of implication for human health and disease, with special attention to mechanisms of Deoxyribonucleic acid (DNA) damage, for example through Ultraviolet (UV) A and B. This has a special resonance for our sunburnt nation. The work, using world class Australian Research Council funded instrumentation, will carry out breakthrough science, exploiting and enhancing existing national strength in biological science with a strong interdisciplinary element. This project will also maintain and enhance Australia's international research profile through its novelty and new overseas collaborations. The project will equip talented young scientists with a spectrum of skills.Read moreRead less
Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of ex ....Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of exposure. Structure determination of biomolecules is at the heart of identifying, diagnosing and potentially developing treatments for diseases, and thus another important reason for studying these interactions is the potential to develop new mass spectrometry based analytical methods.Read moreRead less
Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unch ....Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unchartered area! We will examine the fundamental chemistry (unimolecular and bimolecular reactions) of these systems and build upon some exciting preliminary results which suggest potential applications (e.g. as a proteomics tool to sequence and distinguish between leucine and isoleucine residues in peptides).Read moreRead less
Chemical Synthesis of Bioactive Metabolites and Analogues from Marine Sources and Myxobacteria. This project could result in the production of a new type of anticancer compound. The proposal will study the synthesis of novel natural product analogues that could possess superior biological activities to the natural compounds. In addition, new chemistry may be developed which could be utilised to synthesise a number of related molecules.
Structural modification of conus-derived venom peptides- A route to new therapeutics. Current product deficiencies in the area of pain management are forcing the pharmaceutical industry to develop new strategies for achieving analgesia and reduce their dependence on traditional, addictive opiate-based products. Structural modification of Conus derived peptides will provide exciting new leads for achieving effective analgesia.