Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosph ....Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosphate ester bonds in biological molecules will be developed. Active complexes will be incorporated into nanosized peptide nucleic acid (PNA) - metal complex hybrids and applied as artificial enzymes in the sequence specific cleavage of RNA and DNA. Novel applications of these ?artificial enzymes? in biotechnology are anticipated.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775590
Funder
Australian Research Council
Funding Amount
$200,000.00
Summary
A single crystal X-ray diffractometer with CCD detector for structural analysis of small molecules. In recent years their have been major advances in the capacity of instrumentation to determine the crystal and molecular structure of chemical compounds and materials which in turn has resulted in a rapidly growing understanding of the relationship between the structure of molecules and their function in the design of new materials and as drugs for the treatment of disease and pain. This infrastr ....A single crystal X-ray diffractometer with CCD detector for structural analysis of small molecules. In recent years their have been major advances in the capacity of instrumentation to determine the crystal and molecular structure of chemical compounds and materials which in turn has resulted in a rapidly growing understanding of the relationship between the structure of molecules and their function in the design of new materials and as drugs for the treatment of disease and pain. This infrastructure also provides training of an international standard for undergraduate and post graduate students, thus building the skills capabilities of Australian scientists in the workforce.Read moreRead less
Chemistry of the Transport of Nutrient Copper in Biological Cells. Nutrient trace metals such as copper are needed for enzymes by living organisms but are toxic in excess. Defects in copper metabolism cause Menkes and Wilson diseases in humans and there are direct connections to neurodegenerative diseases (eg, Alzheimer, Parkinson, Creutzfeldt-Jakob, motor neuron diseases). It is crucial to understand how healthy cells control toxic but essential copper so that enlightened intervention is possib ....Chemistry of the Transport of Nutrient Copper in Biological Cells. Nutrient trace metals such as copper are needed for enzymes by living organisms but are toxic in excess. Defects in copper metabolism cause Menkes and Wilson diseases in humans and there are direct connections to neurodegenerative diseases (eg, Alzheimer, Parkinson, Creutzfeldt-Jakob, motor neuron diseases). It is crucial to understand how healthy cells control toxic but essential copper so that enlightened intervention is possible when disturbances of copper metabolism become pathological. The chemistry of key molecules will be studied to reveal their essential properties and thereby to understand the molecular basis of the copper-linked diseases.Read moreRead less
Molecular Characterisation of Metal Transport Proteins. The trace metals are essential to life. The secrets of their catalytic and structural roles are under intensive scrutiny. The molecular mechanisms which regulate concentrations of nutrient metals in biological cells remain poorly understood. Errors in metal metabolism cause disease. For example, defects in copper metabolism cause Menkes and Wilson diseases in humans and there are connections of copper and zinc to neuro-degenerative disea ....Molecular Characterisation of Metal Transport Proteins. The trace metals are essential to life. The secrets of their catalytic and structural roles are under intensive scrutiny. The molecular mechanisms which regulate concentrations of nutrient metals in biological cells remain poorly understood. Errors in metal metabolism cause disease. For example, defects in copper metabolism cause Menkes and Wilson diseases in humans and there are connections of copper and zinc to neuro-degenerative diseases such as Alzheimer and Creutzfeldt-Jakob (mad cow). This project will study the chemistry of metabolic pathways responsible for import of nutrient copper and other metals into biological cells.Read moreRead less
Molecular Probes for Bio-Metals. The nutrient trace metals are essential to life. Problems with the metabolism of iron, copper and zinc are associated with neuro-degenerative diseases such as Alzheimer's, Parkinson's and CJD (Creutzfeldt-Jakob disease). This proposal will develop molecular probes for detection of iron, zinc, copper, manganese and nickel within biological cells. The work will allow examination of the molecular roles of these bio-metals in unprecedented detail and lead to a bette ....Molecular Probes for Bio-Metals. The nutrient trace metals are essential to life. Problems with the metabolism of iron, copper and zinc are associated with neuro-degenerative diseases such as Alzheimer's, Parkinson's and CJD (Creutzfeldt-Jakob disease). This proposal will develop molecular probes for detection of iron, zinc, copper, manganese and nickel within biological cells. The work will allow examination of the molecular roles of these bio-metals in unprecedented detail and lead to a better understanding of their roles in normal metabolism and in disease.Read moreRead less
Nanoprobe and Microprobe Structural and Spectroscopic Studies in Biomedical Research. Breakthrough microprobe and nanoprobe technologies, involving X-ray, visible and infrared light can focus into different components of mammalian cells in order to interrogate the biochemistry that is occurring therein. Each of the different wavelengths of light provides complementary biochemical information that enables multi-layered information on changes in cells that occur as a function of drug treatments a ....Nanoprobe and Microprobe Structural and Spectroscopic Studies in Biomedical Research. Breakthrough microprobe and nanoprobe technologies, involving X-ray, visible and infrared light can focus into different components of mammalian cells in order to interrogate the biochemistry that is occurring therein. Each of the different wavelengths of light provides complementary biochemical information that enables multi-layered information on changes in cells that occur as a function of drug treatments and disease processes. This will provide unprecedented information as to where drugs go and how they are transformed inside cells that, in turn, may revolutionalise the way in which new drugs are designed that have higher specificity and lower side effects.Read moreRead less
Electrochemically Driven Molybdoenzyme Catalysis. Enzymes that catalyse oxidation and reduction reactions need to exchange electrons with their substrate and this supply of electrons needs to be sustained. Artificially reconstituted systems can be developed where the enzyme is coupled with an electrode and the current (electrons) exchanged during the reaction are measured directly. In this project we will reveal whether some unusual and unexplained electrochemical phenomena seen before are relat ....Electrochemically Driven Molybdoenzyme Catalysis. Enzymes that catalyse oxidation and reduction reactions need to exchange electrons with their substrate and this supply of electrons needs to be sustained. Artificially reconstituted systems can be developed where the enzyme is coupled with an electrode and the current (electrons) exchanged during the reaction are measured directly. In this project we will reveal whether some unusual and unexplained electrochemical phenomena seen before are related to the properties of the enzymes themselves or the ways in which their experiments have been conducted.Read moreRead less
Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the a ....Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the area of the Research Priority Goal: Breakthrough Science. Postgraduate research students will be trained in sophisticated state-of-the-art theoretical and synthetic chemical methodologies. The project will enhance Australia's research capability in biological (inorganic) chemistry and promote Australia's standing in the International research community.Read moreRead less
Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has ....Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has potential application in biosensors and biocatalysis.Read moreRead less
Structural studies of catalysis and electron transfer by copper proteins. We propose to determine the crystal structures of five copper-containing proteins. Three are amine oxidases, enzymes that protect a wide range of organisms against toxic cell products (amines). Novel chemical modifications and crystallographic techniques will be used to test hypotheses for the enzyme mechanism. The results will provide a basis for the future manipulation of the enzymes' activities. Our other targets, s ....Structural studies of catalysis and electron transfer by copper proteins. We propose to determine the crystal structures of five copper-containing proteins. Three are amine oxidases, enzymes that protect a wide range of organisms against toxic cell products (amines). Novel chemical modifications and crystallographic techniques will be used to test hypotheses for the enzyme mechanism. The results will provide a basis for the future manipulation of the enzymes' activities. Our other targets, sulfocyanin and auracyanin-A, perform essential electron-transfer functions in an archaeon and a photosynthetic bacterium, respectively. The determination of their molecular structures will answer exciting questions about electron transfer in primitive organisms, and about the evolution of copper proteins as biological electron-transfer agents.Read moreRead less