Covalent Hydrogen Bond Mimetics of Helical Peptide Hormones. Peptide hormones have been identified that adopt a helical shape when bound to their receptor. The project will produce new versions of these hormones by the use of directly bonded chemical linkers in place of the relatively weak helix hydrogen bonds. The resulting hormone mimics will be more stable, have lower molecular weight and be more selective than the natural hormones making them more suitable as drugs. Our new chemical techn ....Covalent Hydrogen Bond Mimetics of Helical Peptide Hormones. Peptide hormones have been identified that adopt a helical shape when bound to their receptor. The project will produce new versions of these hormones by the use of directly bonded chemical linkers in place of the relatively weak helix hydrogen bonds. The resulting hormone mimics will be more stable, have lower molecular weight and be more selective than the natural hormones making them more suitable as drugs. Our new chemical techniques allow us for the first time to fully investigate this approach which if successful will be applicable to many other helical peptides and therefore could be an important drug development technique.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0233459
Funder
Australian Research Council
Funding Amount
$136,000.00
Summary
High Pressure Chemistry Facility. High pressure is a mild, clean and high yielding method of promoting a variety of important chemical reactions. This proposal seeks equipment to conduct such reactions on a pilot and large scale or in large numbers (high-pressure combinatorial chemistry). This equipment would be unique in the Southern Hemsiphere and, together with existing infrastructure, creates an Australian centre in high pressure, liquid - phase chemistry. It would support research programm ....High Pressure Chemistry Facility. High pressure is a mild, clean and high yielding method of promoting a variety of important chemical reactions. This proposal seeks equipment to conduct such reactions on a pilot and large scale or in large numbers (high-pressure combinatorial chemistry). This equipment would be unique in the Southern Hemsiphere and, together with existing infrastructure, creates an Australian centre in high pressure, liquid - phase chemistry. It would support research programmes aimed at developing new materials for microelectronic components and new compounds for high through-put drug discovery and insecticide discovery programmes.Read moreRead less
Neurotrophic Active Natural Products: Total Synthesis and Biological Evaluation of Neovibsanins A and B, and Analogues. New chemical entities (drug candidates) that promote neurite outgrowth have significant ramifications to mankind as they have real potential to repair damaged, or grow replacement, nerve cells affected by neuro and central nervous system (CNS) degenerative disease (e.g. Alzhiemer's, Parkinson's, Huntington's etc). This scientific endeavour will reveal new drug like molecules fo ....Neurotrophic Active Natural Products: Total Synthesis and Biological Evaluation of Neovibsanins A and B, and Analogues. New chemical entities (drug candidates) that promote neurite outgrowth have significant ramifications to mankind as they have real potential to repair damaged, or grow replacement, nerve cells affected by neuro and central nervous system (CNS) degenerative disease (e.g. Alzhiemer's, Parkinson's, Huntington's etc). This scientific endeavour will reveal new drug like molecules for potential biological and clinical application, thereby assisting a substantial proportion of Australians suffering from these debilitating diseases. Read moreRead less
Probing the Interface Between Polymeric Photonic Materials and Biology. This application provides a basis for Professor A. B. Holmes to develop a collaboration between the University of Melbourne (within the Bio21 Institute initiative) and CSIRO Division of Molecular Science to prepare novel plastics for electronics applications (lap top displays, transistors and solar cells) and to make specialised macromolecules for studying the way in which biological molecules may be made to recognise other ....Probing the Interface Between Polymeric Photonic Materials and Biology. This application provides a basis for Professor A. B. Holmes to develop a collaboration between the University of Melbourne (within the Bio21 Institute initiative) and CSIRO Division of Molecular Science to prepare novel plastics for electronics applications (lap top displays, transistors and solar cells) and to make specialised macromolecules for studying the way in which biological molecules may be made to recognise other molecules and thus change their function. It is envisaged that the multidisciplinary research collaboration will lead to commercial opportunities in "plastic electronics" and in human health such as the control of cancer and infectious diseases.Read moreRead less
Study the Utility of Novel Drug Polymer Conjugates. The products likely to arise from the technology described in this proposal could have application in medical, veterinary and agricultural industries. It offers the potential to treat diseases that are at present poorly treated by enabling delivery direct to the diseased organ (e.g. eye - bacterial endophthalmitis). Completion of the project will also assist a fledgling biotech company transition to a development company with a multiple produ ....Study the Utility of Novel Drug Polymer Conjugates. The products likely to arise from the technology described in this proposal could have application in medical, veterinary and agricultural industries. It offers the potential to treat diseases that are at present poorly treated by enabling delivery direct to the diseased organ (e.g. eye - bacterial endophthalmitis). Completion of the project will also assist a fledgling biotech company transition to a development company with a multiple product portfolio, which will have a direct economic benefit to Australia both in terms of potential export earnings and as an employer highly skilled staff. The project will also provide research training and career opportunities for developing Australian based researchers.Read moreRead less
Synthesis and evaluation of anti-microbial porphyrin adducts for the targeted inhibition of Porphyromonas gingivalis. At present the effectiveness of therapy for inflammatory disease of the gum tissue (periodontitis) is limited by the lack of a selective anti-microbial agent. The investigators have discovered a novel mechanism of binding of the blood product porphyrin by a unique receptor of a key pathogen implicated in this disease. By exploiting this knowledge a modified porphyrin linked to an ....Synthesis and evaluation of anti-microbial porphyrin adducts for the targeted inhibition of Porphyromonas gingivalis. At present the effectiveness of therapy for inflammatory disease of the gum tissue (periodontitis) is limited by the lack of a selective anti-microbial agent. The investigators have discovered a novel mechanism of binding of the blood product porphyrin by a unique receptor of a key pathogen implicated in this disease. By exploiting this knowledge a modified porphyrin linked to an antibiotic was shown to have a selective effect on the target organism. Refinement of this complex has the potential to provide a clinically useful, selective agent.Read moreRead less
Development of a Diversity-Oriented Synthesis Platform. Genomic, proteomic and other studies of the molecular basis of disease are providing a constant stream of biomolecular targets for drug discovery. Identifying suitable drugs candidates to affect these targets centres around procuring a suitable library of compounds for screening. This application addresses some of the key issues related to the development of appropriate compound libraries for such screening programs.
Synthesis of Novel Dual Acting, Selenium Containing Antioxidants. Ischemic heart disease and chronic inflammation afflict a large segment of the Australian population, especially the ageing. These states are associated with free-radicals and other reactive oxygen species and can be controlled to some extent by the application of adenosine therapy. This project will combine the activity of adenosine agonists and enhancers with selenium-containing antioxidants, used to quench reactive oxygen spe ....Synthesis of Novel Dual Acting, Selenium Containing Antioxidants. Ischemic heart disease and chronic inflammation afflict a large segment of the Australian population, especially the ageing. These states are associated with free-radicals and other reactive oxygen species and can be controlled to some extent by the application of adenosine therapy. This project will combine the activity of adenosine agonists and enhancers with selenium-containing antioxidants, used to quench reactive oxygen species, to provide a powerful new class of pharmaceutical products designed to enhance the quality of life of Australians afflicted by diseases propagated by free-radicals.Read moreRead less
Chemical Synthesis of Bioactive Metabolites and Analogues from Marine Sources and Myxobacteria. This project could result in the production of a new type of anticancer compound. The proposal will study the synthesis of novel natural product analogues that could possess superior biological activities to the natural compounds. In addition, new chemistry may be developed which could be utilised to synthesise a number of related molecules.
Development of Liposaccharide Peptide Conjugates for Peptide Drug Delivery. We aim to adapt the Solid Phase Oligosaccharide Synthesis technology patented by Alchemia to develop methodologies that will allow the assembly of sugar, lipid and peptide units on a single solid phase resin. This synthetic technology will then be used to generate a library of liposaccharide conjugates of two model peptides (LHRH and TRH) to investigate and optimise a broadly applicable peptide drug delivery system whic ....Development of Liposaccharide Peptide Conjugates for Peptide Drug Delivery. We aim to adapt the Solid Phase Oligosaccharide Synthesis technology patented by Alchemia to develop methodologies that will allow the assembly of sugar, lipid and peptide units on a single solid phase resin. This synthetic technology will then be used to generate a library of liposaccharide conjugates of two model peptides (LHRH and TRH) to investigate and optimise a broadly applicable peptide drug delivery system which improves peptides oral absorption, metabolic stability and bioavailability.Read moreRead less