Dissecting catalysis and inhibition of a unique endo-acting mannose-processing glycosidase. Defects in the attachment of carbohydrates to proteins are a hallmark of diseases such as cancer and viral infection. This project will dissect the molecular details of the bond-making and breaking steps that occur during the synthesis of glycoproteins assisting in the development of innovative new drugs.
Electrophile induced domino reaction sequences with ion-pair chiral induction. In this project, new catalysts and procedures will be developed to improve our capacity to access and modify the structure and properties of complex molecules. These methods will be used to gain access to a number of bioactive natural products in order to better evaluate and develop their therapeutic potential.
Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this pro ....Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this project will deliver natural and new compounds for analysis of anti-cancer activity. The rewards of the development of new synthetic methods are enormous for the community and in the education of our scientists.Read moreRead less
Breaking it down: Dissecting the mechanism and exploring new inhibition strategies for polysaccharide cleaving enzymes. Mannose, a common carbohydrate building block, is present in a wide variety of complex polysaccharides including energy storage polymers and glycans attached to proteins. The enzymes that degrade these mannose-rich polymers, termed mannosidases, are important in biofuel production and human health and disease. This project will study a range of mannosidases to chemically and st ....Breaking it down: Dissecting the mechanism and exploring new inhibition strategies for polysaccharide cleaving enzymes. Mannose, a common carbohydrate building block, is present in a wide variety of complex polysaccharides including energy storage polymers and glycans attached to proteins. The enzymes that degrade these mannose-rich polymers, termed mannosidases, are important in biofuel production and human health and disease. This project will study a range of mannosidases to chemically and structurally define their mechanisms and establish strategies to allow intervention in mannosidase-specific disease processes. This work will inform strategies to engineer new enzymes for future biotechnology and industrial applications including sustainable chemical manufacturing, and underpin the development of innovative drugs for treating fungal infections and cancer.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.
Identifying mitogenic signalling proteins with phosphatidyl inositol lipids. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids attached to 'fishing lines' we can search for, identify and study the function of all the downstream signalling proteins in activated c ....Identifying mitogenic signalling proteins with phosphatidyl inositol lipids. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids attached to 'fishing lines' we can search for, identify and study the function of all the downstream signalling proteins in activated cancer cells. This will provide the basic information for drug discovery processes to target specific molecules that inhibit and control the function of the signalling proteins implicated in the growth of cancer cells.Read moreRead less
Synthesis of phosphatidylinositol and inositol polyphosphate derivatives to probe key signalling proteins associated with cell growth and cancer. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids and inositol polyphosphates attached to 'fishing lines' we can sea ....Synthesis of phosphatidylinositol and inositol polyphosphate derivatives to probe key signalling proteins associated with cell growth and cancer. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids and inositol polyphosphates attached to 'fishing lines' we can search for, identify and study the function of many of the downstream signalling proteins in activated cancer cells. This will provide the basic information for discovery processes to target specific molecules that inhibit and control the function of the signalling proteins implicated in the growth of cancer cells.Read moreRead less
Inhibition of membrane-bound carbonic anhydrases with small molecules as a novel approach to target a safe and effective treatment for solid tumours. Over 85 per cent of human cancers are solid tumours and the prognosis for patients with advanced solid tumours is extremely poor owing to resistance to conventional chemo- and radio- therapies. Our research will underpin the development of new, safe and effective drug treatment options for cancer patients with solid tumours.
Chiral Catalysts by Rational Design. This project aims to integrate theory and experiment to design new catalysts for the synthesis of multi-stereocentre-containing molecules. Such molecules offer clear advantages in the area of drug design, owing to their potent and selective binding to biological targets, but a lack of available methods for their preparation currently limits their widespread use. This project will use theory to guide the discovery of new ways to make these molecules. It is exp ....Chiral Catalysts by Rational Design. This project aims to integrate theory and experiment to design new catalysts for the synthesis of multi-stereocentre-containing molecules. Such molecules offer clear advantages in the area of drug design, owing to their potent and selective binding to biological targets, but a lack of available methods for their preparation currently limits their widespread use. This project will use theory to guide the discovery of new ways to make these molecules. It is expected that detailed understanding of the factors that control stereocentre formation will be obtained from accurate theoretical modelling and will be applied to invent new catalysts that deliver improved performance and control over product structure.Read moreRead less