Solid phase synthesis of side-chain cross-linked peptide oligomers. This research will provide a unique opportunity to investigate the biological pathways and causative factors leading to diseases such as Alzheimer’s disease. Such information will guide the design and development of therapeutic strategies and diagnostic reagents.
Thioamide ligations: new technologies for peptide and protein synthesis. This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and ....Thioamide ligations: new technologies for peptide and protein synthesis. This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and proteins will also be developed. The outcomes of this research will lead to breakthroughs in synthetic methodologies for the assembly and functionalisation of peptides and proteins, thereby enabling access to a range of homogeneous, post translationally modified proteins though total chemical synthesis. These research outcomes will expand Australia's research capability and global competitiveness in the field of biotechnology, delivering significant benefits to the third largest manufacturing sector in Australia.Read moreRead less
Solid-phase synthesis of sulfopeptides for evaluation of chemokine-receptor recognition. This research program will develop new chemical methods for preparing biologically active molecules that contain sulphate. These molecules have important functions in controlling blood clotting, hormone activity, immune responses, and AIDS or malarial infection. The new chemical methods will be used to study the interactions of two groups of proteins that control the movement of white blood cells in inflamma ....Solid-phase synthesis of sulfopeptides for evaluation of chemokine-receptor recognition. This research program will develop new chemical methods for preparing biologically active molecules that contain sulphate. These molecules have important functions in controlling blood clotting, hormone activity, immune responses, and AIDS or malarial infection. The new chemical methods will be used to study the interactions of two groups of proteins that control the movement of white blood cells in inflammatory responses. The research will provide insights into the biochemistry of inflammation and will contribute to the development of new therapies for diseases affecting young Australians (allergy, asthma, and viral infections) as well as the elderly (atherosclerosis and arthritis).Read moreRead less
Development and application of new peptide ligation methods for the synthesis and structure-function studies of glycoproteins. Novel synthetic technologies will be developed in this project to facilitate the preparation of glycoproteins, which are of widespread biological and therapeutic interest. These methods will enable the preparation of pure glycoproteins for detailed biochemical and functional studies eventually leading to therapeutic and diagnostic applications.
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
Functional studies of tyrosine sulfation using synthetic sulfoproteins. This project aims to address a lack of knowledge about how post-translational sulfation of tyrosine residues influences protein function. The project will develop a synthetic platform for the rapid and efficient generation of libraries of site-selectively sulfated proteins. The new methods will be used to study bioactive sulfated proteins secreted by ticks that dampen the inflammatory response and prevent blood from clotting ....Functional studies of tyrosine sulfation using synthetic sulfoproteins. This project aims to address a lack of knowledge about how post-translational sulfation of tyrosine residues influences protein function. The project will develop a synthetic platform for the rapid and efficient generation of libraries of site-selectively sulfated proteins. The new methods will be used to study bioactive sulfated proteins secreted by ticks that dampen the inflammatory response and prevent blood from clotting. Underpinned by the ability to access synthetic sulfoproteins, expected outcomes include a detailed understanding of how tyrosine sulfation can modulate function and stability of antibodies and proteins with anticoagulant and anti-inflammatory activities. Significant benefits of the project will include breakthrough technologies for the preparation of homogeneously modified proteins, which will strengthen Australia’s growing biotechnology sector.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
Defining the biosynthesis and immunological properties of complex bacterial glycolipids. We will study how sugar-lipids are made by industrially, agriculturally and medically important bacteria, and how they interact with the immune system. This will provide new insights into cell wall biosynthesis of importance to the biotechnology industry and identify new reagents for manipulating the immune system.
In vivo molecular imaging using engineered affinity reagents and fluorescent laser scanning confocal endomicroscopy. The goal of this project is to develop laser scanning confocal endomicroscopy as a tool for basic scientific discovery and rapid detection of disease biomarkers. The cutting-edge instrument and associated technologies will provide scientists with unprecedented access to dynamic biological processes as they occur in real-time. In addition, it will enable the development of virtual ....In vivo molecular imaging using engineered affinity reagents and fluorescent laser scanning confocal endomicroscopy. The goal of this project is to develop laser scanning confocal endomicroscopy as a tool for basic scientific discovery and rapid detection of disease biomarkers. The cutting-edge instrument and associated technologies will provide scientists with unprecedented access to dynamic biological processes as they occur in real-time. In addition, it will enable the development of virtual biopsies and instant diagnosis without the need for costly and time-consuming histopathological reports. Thus, it will not only drive transformative research but also transform health care delivery. It will also be a major boost to the Australian biotechnology industry with potential for enormous economic benefits.Read moreRead less
New methods for the chemical synthesis of a library of glycopeptide-based tri-component cancer vaccines. A novel method for the synthesis of tumour-associated glycopeptides will be developed in this research as well as the preparation of a library of glycopeptide-based cancer vaccines. These vaccines will be tested in immunological studies with a view to elucidating new immune-based therapies for the treatment of cancer.