Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for ....Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for the construction and modification of peptides and proteins by harnessing the energy in a unique class of strained molecules. A focus on peptide-based inhibitors of the proteasome, a critical target for modern cancer treatments, should provide future health and economic benefits for the Australian community.Read moreRead less
Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic be ....Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic benefits for the Australian community, including: the first approach to a class of promising antibiotic peptide natural product analogues, the development of a mild electrochemical approach to peptide modification, and the production of a library of novel amino acids for incorporation into potential antibiotic leads.Read moreRead less
Time to shine for constrained peptides as next-generation pharmaceuticals. Current methods for the screening and generation of peptide and protein drugs are laborious, expensive and often incompatible with the biological systems used in pharmaceutical industries. Leveraging recent advancements in chemistry and molecular biology, this project aims to improve the design, synthesis and screening of peptide-based pharmaceuticals. Key research outcomes are innovative biocompatible chemical transforma ....Time to shine for constrained peptides as next-generation pharmaceuticals. Current methods for the screening and generation of peptide and protein drugs are laborious, expensive and often incompatible with the biological systems used in pharmaceutical industries. Leveraging recent advancements in chemistry and molecular biology, this project aims to improve the design, synthesis and screening of peptide-based pharmaceuticals. Key research outcomes are innovative biocompatible chemical transformations for the screening of large peptide libraries, to unleash the revolutionary potential of constrained peptides in drug development. Expected benefits are reliable and cost-effective technologies for the rapid production of biologically active molecules for future targeted use in human and agricultural pharmaceuticals.Read moreRead less
A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societa ....A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societal benefit as a fundamental scientific platform, improving Australia's capacity and impact in the agriculture and the healthcare sectors. The platform technology has the potential to increase the quality of life for patients and their carers, while also produce fitter, healthier livestock.Read moreRead less
Earth Abundant Metal Complexes for Nitrogen Activation. This project aims to develop a range of complexes based around earth abundant metals that are capable of activating nitrogen (N2) at ambient pressure and temperature. The project expects to generate new knowledge in the area of organometallic chemistry, specifically with regards to molecular metal-metal bonding and subsequent reactivity towards the activation of nitrogen. The activation of atmospheric nitrogen is performed on a multi-millio ....Earth Abundant Metal Complexes for Nitrogen Activation. This project aims to develop a range of complexes based around earth abundant metals that are capable of activating nitrogen (N2) at ambient pressure and temperature. The project expects to generate new knowledge in the area of organometallic chemistry, specifically with regards to molecular metal-metal bonding and subsequent reactivity towards the activation of nitrogen. The activation of atmospheric nitrogen is performed on a multi-million tonne scale each year and is key to a number of industrial processes. As such, investigations into new and improved catalysts for this process would potentially bring huge financial benefits to industry, as well as benefiting the environment by reducing energy demand and associated climate change.Read moreRead less
Self-assembled supramolecular cages for guest binding and catalysis. This project aims to construct a family of supramolecular metal-containing cage-shaped molecules that possess specialised binding pockets with unique chemical properties that mimic enzymes. Many existing cage molecules contain well-defined three dimensional cavities reminiscent of enzymes' active sites. However, unlike natural systems they do not contain "active" metals with free coordination sites, and this limits their cataly ....Self-assembled supramolecular cages for guest binding and catalysis. This project aims to construct a family of supramolecular metal-containing cage-shaped molecules that possess specialised binding pockets with unique chemical properties that mimic enzymes. Many existing cage molecules contain well-defined three dimensional cavities reminiscent of enzymes' active sites. However, unlike natural systems they do not contain "active" metals with free coordination sites, and this limits their catalytic ability. This project aims to prepare a large family of robust organic cages quickly and easily, and subsequently incorporate metals containing free active sites that point into the cage cavity. It is expected that this will deliver strong and selective guest binding, and efficient and selective catalysis.Read moreRead less
Next generation supramolecular frameworks. This project aims to prepare new supramolecular frameworks assembled by hydrogen or halogen bonds. It is anticipated that this work will increase fundamental understanding of supramolecular self-assembly processes and the dynamic processes that are possible within these rearrangeable systems. The project aims to prepare a family of related frameworks, which will allow a detailed comparison of the stability, porosity and biotechnological applicability of ....Next generation supramolecular frameworks. This project aims to prepare new supramolecular frameworks assembled by hydrogen or halogen bonds. It is anticipated that this work will increase fundamental understanding of supramolecular self-assembly processes and the dynamic processes that are possible within these rearrangeable systems. The project aims to prepare a family of related frameworks, which will allow a detailed comparison of the stability, porosity and biotechnological applicability of new supramolecular materials. The expected outcomes are the development of lightweight and benign organic systems that will have applications in the removal of toxic organic and heavy metal pollutants from water, and in the encapsulation and stabilisation of catalytically-active enzymes.Read moreRead less
Boryl Pincers and Beyond: Taming Borometallic Chemistry. Industrial applications of coordination complexes in catalysis reduce energy input and environmental impact but almost exclusively involve classical donors such as nitrogen, oxygen, sulfur and phosphorus. Boron, whilst prevalent and environmentally benign, is under-utilised in such applications, in part due to the high reactivity of the metal boron bond.
This research will seek to tame and then exploit the unique features of boron within p ....Boryl Pincers and Beyond: Taming Borometallic Chemistry. Industrial applications of coordination complexes in catalysis reduce energy input and environmental impact but almost exclusively involve classical donors such as nitrogen, oxygen, sulfur and phosphorus. Boron, whilst prevalent and environmentally benign, is under-utilised in such applications, in part due to the high reactivity of the metal boron bond.
This research will seek to tame and then exploit the unique features of boron within pincer ligand frameworks in metal coordination complexes, with particular attention focusing on, but not limited to catalytic alkyne metathesis.Read moreRead less
Mixed-Metal Clusters for Catalysis and Optical Applications. This project aims to afford new heterometallic molecular materials as precursors to catalysts and as new optical materials, exploiting oxophilic and carbophilic transition metal atoms for synergistic cooperation in certain catalytic processes, and using the polarity of heterometallic bonds to achieve strong optical limiting. Expected outcomes of this project include cluster structure/composition - catalysis/optical properties correlati ....Mixed-Metal Clusters for Catalysis and Optical Applications. This project aims to afford new heterometallic molecular materials as precursors to catalysts and as new optical materials, exploiting oxophilic and carbophilic transition metal atoms for synergistic cooperation in certain catalytic processes, and using the polarity of heterometallic bonds to achieve strong optical limiting. Expected outcomes of this project include cluster structure/composition - catalysis/optical properties correlations that will signpost the route to efficient catalysts and optical limiters. This Project should provide significant benefits such as chemoselective catalysts needed for pharmaceutical drug and agricultural chemical production, and broad temporal range optical limiters needed for optical device protection.Read moreRead less