Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research p ....Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research program using a number of novel chemical technologies. These glycoproteins will be used to develop cancer vaccines and diagnostics. Cancer is a severe burden on the Australian community and on the economy, therefore this research will be of significant benefit to Australia.Read moreRead less
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
Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to sy ....Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to synthesise sex pheromones. We propose that understanding the chemical and biochemical steps employed by the flies will allow us to design inhibitors to prevent pheromone production and thus provide a novel, species specific method for controlling fruit flies.Read moreRead less
Defining peptide structure and function: the shape of things to come. In this project we develop new and general ways of chemically defining the structure and function of natural peptides. This then provides a basis of potential therapies to treat a number of diseases currently confronting Australia's aging population, for example, cataract, Alzheimer's disease, cancer, and cardiovascular disease.
Unlocking the secret chemistry of organosulfur biodegradation. The element sulfur is essential for life. Its transformation between organic-sulfur compounds to inorganic forms is a crucial part of the biogeochemical cycle. This project will elucidate the molecular details of the final leg of the biosulfur cycle: organosulfur breakdown into mineral form. An integrated chemical and biochemical approach will be used to illuminate how the carbon-sulfur bond is broken. This project will deliver a det ....Unlocking the secret chemistry of organosulfur biodegradation. The element sulfur is essential for life. Its transformation between organic-sulfur compounds to inorganic forms is a crucial part of the biogeochemical cycle. This project will elucidate the molecular details of the final leg of the biosulfur cycle: organosulfur breakdown into mineral form. An integrated chemical and biochemical approach will be used to illuminate how the carbon-sulfur bond is broken. This project will deliver a detailed molecular understanding of organosulfur breakdown to permit organosulfur recycling. Benefits of this research include potential biotechnology applications for breaking down xenobiotic organosulfonates and sustainable approaches to reduce dependence on agricultural fertilisers.Read moreRead less
A bio-enabled synthesis for the glycopeptide antibiotics. This project aims to develop an in vitro biomimetic synthesis for glycopeptide antibiotics (GPAs) by combining peptide synthesis and crosslinking catalysed by biosynthetic Cytochrome P450 enzymes. The crosslinking step in GPA biosynthesis is essential for antibiotic activity but impedes their chemical synthesis. This project will study the in vitro behaviour and characteristics of the biosynthetic P450 enzymes. This will provide direct be ....A bio-enabled synthesis for the glycopeptide antibiotics. This project aims to develop an in vitro biomimetic synthesis for glycopeptide antibiotics (GPAs) by combining peptide synthesis and crosslinking catalysed by biosynthetic Cytochrome P450 enzymes. The crosslinking step in GPA biosynthesis is essential for antibiotic activity but impedes their chemical synthesis. This project will study the in vitro behaviour and characteristics of the biosynthetic P450 enzymes. This will provide direct benefits: the development of new glycopeptide antibiotic derivatives and the identification of new biocatalysts for complex chemical synthesis. Knowledge gained will also directly enable future reengineering of glycopeptide antibiotic production in vivo.Read moreRead less
Understanding the mechanism of two important cytochrome P450 catalysed reactions: dehydrogenation and C-C cleavage. Cytochromes P450 are enzymes that play key roles in drug metabolism and biosynthesis. P450s often catalyse hydroxylation but also carry out important transformations such as dehydrogenation or carbon-carbon bond cleavage. Such reactions are pivotal in many biological pathways. This work will elucidate the mechanism of these transformations and the factors that facilitate their occu ....Understanding the mechanism of two important cytochrome P450 catalysed reactions: dehydrogenation and C-C cleavage. Cytochromes P450 are enzymes that play key roles in drug metabolism and biosynthesis. P450s often catalyse hydroxylation but also carry out important transformations such as dehydrogenation or carbon-carbon bond cleavage. Such reactions are pivotal in many biological pathways. This work will elucidate the mechanism of these transformations and the factors that facilitate their occurrence. This will mainly entail the synthesis of small organic mechanistic probes and determining the structure and stereochemistry of the product of enzymic oxidation. Understanding these mechanisms will allow us to predict when such reactions will occur, enabling their utilisation in for example drug design in the avoidance of the formation of toxic metabolites.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.