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.
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 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.
Discovery Early Career Researcher Award - Grant ID: DE140101632
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Development of Innovative Chemical Tools for Studying Glycosyltransferases . This project aims to develop chemical probes capable of selectively binding and inhibiting two classes of carbohydrate processing enzymes known as O-linked beta-N-acetylglucosamine transferase and sialyltransferases. These enzymes are overexpressed in various cancers and play critical roles in cancer progression. Probes will be developed to analyse the activities of these enzymes in cancer cells.
Discovery Early Career Researcher Award - Grant ID: DE150101863
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Strained alkenes as chemical probes for cysteine sulfenic acid. This project aims to introduce strained alkenes as probes for cysteine sulfenic acid, a poorly understood biomarker for oxidative stress. This probe will enable rapid detection of cysteine sulfenic acid and meet an urgent need for tools to map cysteine redox signalling. Moreover, since many enzymes feature a cysteine sulfenic acid at their active site, the strained alkene probes will also serve as useful inhibitor probes of these en ....Strained alkenes as chemical probes for cysteine sulfenic acid. This project aims to introduce strained alkenes as probes for cysteine sulfenic acid, a poorly understood biomarker for oxidative stress. This probe will enable rapid detection of cysteine sulfenic acid and meet an urgent need for tools to map cysteine redox signalling. Moreover, since many enzymes feature a cysteine sulfenic acid at their active site, the strained alkene probes will also serve as useful inhibitor probes of these enzymes. Such inhibitor probes will provide critical information for potential therapeutic applications in human conditions associated with oxidative stress such as ageing, cancer, and heart disease.Read moreRead less
New peptide ligation technology for the rapid assembly of modified proteins. The project aims to develop novel technologies to enable the synthesis of modified proteins that are of widespread biological and therapeutic interest. More than 70 per cent of all human proteins are modified with a range of functionalities after translation from the ribosome. Although these modifications are of crucial importance for biological activity, characterising the effect of a given modification on function is ....New peptide ligation technology for the rapid assembly of modified proteins. The project aims to develop novel technologies to enable the synthesis of modified proteins that are of widespread biological and therapeutic interest. More than 70 per cent of all human proteins are modified with a range of functionalities after translation from the ribosome. Although these modifications are of crucial importance for biological activity, characterising the effect of a given modification on function is difficult due to problems in obtaining the protein in pure form. The goal of this project is to develop a peptide ligation methodology to access pure modified proteins in a rapid manner through the exploitation of a new reaction recently discovered in our laboratory. The project plans to explore the scope and mechanism of the new reaction as well as its application in the total chemical synthesis and structure-function studies of important modified proteins.Read moreRead less
Fine-tuning the conformations of cyclic peptides: a paradigm for optimising synthetic efficiency and biological activity. This proposal develops a strategy for optimising the synthesis and properties of an important class of drug molecules known as cyclic peptides. Such molecules show great promise as therapeutic agents, but they can be very difficult to synthesise and their three-dimensional shapes can be difficult to control. This project simultaneously addresses both of these problems, by exp ....Fine-tuning the conformations of cyclic peptides: a paradigm for optimising synthetic efficiency and biological activity. This proposal develops a strategy for optimising the synthesis and properties of an important class of drug molecules known as cyclic peptides. Such molecules show great promise as therapeutic agents, but they can be very difficult to synthesise and their three-dimensional shapes can be difficult to control. This project simultaneously addresses both of these problems, by exploiting a series of unusual amino acid building blocks that have a variety of shapes and different levels of conformational flexibility. This strategy will enable the development of a wide variety of therapeutically-relevant cyclic peptides, and to exemplify this concept a panel of cyclic peptides will be created that are specifically targeted for activity against solid tumours.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.
Synthesis and Structure-Function Studies of the Glycoprotein Adiponectin. This project aims to understand the role of carbohydrate modifications on the structure and function of the fat cell-derived hormone adiponectin, which has shown protective effects against obesity, type 2 diabetes and cardiovascular disease. Advancing knowledge of the molecular mechanisms that regulate fat is crucial to unravelling the processes involved in the development of these diseases. The project plans to use novel ....Synthesis and Structure-Function Studies of the Glycoprotein Adiponectin. This project aims to understand the role of carbohydrate modifications on the structure and function of the fat cell-derived hormone adiponectin, which has shown protective effects against obesity, type 2 diabetes and cardiovascular disease. Advancing knowledge of the molecular mechanisms that regulate fat is crucial to unravelling the processes involved in the development of these diseases. The project plans to use novel synthetic technologies to access a library of adiponectins with defined patterns of carbohydrates attached to the peptide backbone, thus potentially enabling detailed dissection of the role of these modifications on structure, cell signalling and insulin sensitising activities.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100222
Funder
Australian Research Council
Funding Amount
$180,000.00
Summary
Advanced stopped flow: electron paramagnetic resonance apparatus for measurement of short-lived free radicals in engineering, science and medicine. The facility will enable world class research into complex chemical processes relevant to industry, environmental science and biochemistry. This will result in development of new technologies in explosives, pollution reduction and energy storage, and enhance our understanding of chemical processes that lead to sperm deoxyribonucleic acid (DNA) damage ....Advanced stopped flow: electron paramagnetic resonance apparatus for measurement of short-lived free radicals in engineering, science and medicine. The facility will enable world class research into complex chemical processes relevant to industry, environmental science and biochemistry. This will result in development of new technologies in explosives, pollution reduction and energy storage, and enhance our understanding of chemical processes that lead to sperm deoxyribonucleic acid (DNA) damage and infertility.Read moreRead less