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
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
Discovery Early Career Researcher Award - Grant ID: DE130101673
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Access to biomimetic carbohydrate receptors using dynamic combinatorial chemistry. This project aims to utilise novel synthetic technology for the development of cyclic peptide libraries as novel drug leads for the treatment of Dengue virus, HIV and cancer.
Discovery Early Career Researcher Award - Grant ID: DE220101329
Funder
Australian Research Council
Funding Amount
$435,000.00
Summary
Advanced Chemical Protein Synthesis and Applications. This project aims to develop enhanced methods for the chemical assembly of peptides, oligonucleotides and proteins. This will lead to the creation of new knowledge in chemistry and structural biology, and underpin advances in the drug discovery process, pharmaceutical manufacture and biocatalysis. Once complete, it is expected that lower cost, greener processes for manufacturing drugs such as Enfuvirtide (for HIV) will ensue. A new generatio ....Advanced Chemical Protein Synthesis and Applications. This project aims to develop enhanced methods for the chemical assembly of peptides, oligonucleotides and proteins. This will lead to the creation of new knowledge in chemistry and structural biology, and underpin advances in the drug discovery process, pharmaceutical manufacture and biocatalysis. Once complete, it is expected that lower cost, greener processes for manufacturing drugs such as Enfuvirtide (for HIV) will ensue. A new generation of hyper-stable, environmentally friendly catalysts will also be developed. This could enable domestic production of fine chemicals and essential medicines, and thus create high-tech jobs in a more diversified, resilient economy. Ultimately, it could lead to improved outcomes in human health.Read moreRead less
New Conus-derived alpha-conotoxin analgesics for the treatment of chronic pain: structure, mode of action, delivery and disposition. 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 cone snail derived peptides will provide exciting new leads for achieving effective analgesia.
ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the d ....ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the design of peptides and proteins for targeted scientific, agricultural, biotechnology, animal health and pharmaceutical applications. CIPPS will assemble leading researchers from diverse disciplines to create a sustainable national entity that will drive new Australian industries and train next generation researchers.Read moreRead less