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Synthetic compounds to specifically activate or inhibit ryanodine receptor calcium ion channels. The aim of the project is develop synthetic compounds that specifically and reversibly activate or inhibit ryanodine receptor calcium release channels, and will thus increase or reduce the force developed by skeletal muscle and the heart. The compounds will be useful in biomedical and veterinary sciences and in the livestock industry. Some of the compounds that are not effective on mammalian ryan ....Synthetic compounds to specifically activate or inhibit ryanodine receptor calcium ion channels. The aim of the project is develop synthetic compounds that specifically and reversibly activate or inhibit ryanodine receptor calcium release channels, and will thus increase or reduce the force developed by skeletal muscle and the heart. The compounds will be useful in biomedical and veterinary sciences and in the livestock industry. Some of the compounds that are not effective on mammalian ryandine receptor isoforms might interact with insect channels and provide a template for a new class of insecticides. The compounds will be based on naturally occurring peptides which specifically and reversibly modulate mammalian calcium channels.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883096
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Analytical and Preparative Enantioselective Chromatography. Enantiomers are forms of the same molecule that are non-superimposable mirror images of one another, like a left hand and a right hand. Because they are so similar they are very difficult to separate. However, they have very different biological properties, such as when used as drugs. One enantiomer may be beneficial while the other has no effect or sometimes is even toxic. Therefore it is important to be able to tell how much of ea ....Analytical and Preparative Enantioselective Chromatography. Enantiomers are forms of the same molecule that are non-superimposable mirror images of one another, like a left hand and a right hand. Because they are so similar they are very difficult to separate. However, they have very different biological properties, such as when used as drugs. One enantiomer may be beneficial while the other has no effect or sometimes is even toxic. Therefore it is important to be able to tell how much of each enantiomer is present in a sample and to be able to separate them. This facility will allow us to do both of these things.Read moreRead less
Amino Acid and Peptide Radicals in Biochemistry and Synthesis. The aim of this research is to develop a better fundamental understanding of biochemical free radical reactions of peptides and proteins, particularly those involving superoxide radical anion and thiols, and peptide radicals in enzyme-catalysed reactions. Knowledge gained through this work will be used in the synthesis of physiologically active amino acids and peptides, as well as to establish ways to regulate biochemical free radic ....Amino Acid and Peptide Radicals in Biochemistry and Synthesis. The aim of this research is to develop a better fundamental understanding of biochemical free radical reactions of peptides and proteins, particularly those involving superoxide radical anion and thiols, and peptide radicals in enzyme-catalysed reactions. Knowledge gained through this work will be used in the synthesis of physiologically active amino acids and peptides, as well as to establish ways to regulate biochemical free radical processes. The ultimate goal of the research is to develop methods and pharmaceutical compounds to prevent and treat human disorders associated with these reactions, and to underpin commercial exploitation of peptide and protein biomaterials.Read moreRead less
Development of Chemoenzymatic Methods for the Selective Elaboration of Polyfunctionalised Therapeutic Agents to Oligomers with Improved Efficacy. The aims of the project are to screen a novel collection of genetically engineered enzymes for their capacity to selectively manipulate proven therapeutic agents so that, ultimately, much more potent polymeric derivatives of the agent/drug can be obtained. The combined use of enzyme libraries and chemical manipulations to generate more powerful polymer ....Development of Chemoenzymatic Methods for the Selective Elaboration of Polyfunctionalised Therapeutic Agents to Oligomers with Improved Efficacy. The aims of the project are to screen a novel collection of genetically engineered enzymes for their capacity to selectively manipulate proven therapeutic agents so that, ultimately, much more potent polymeric derivatives of the agent/drug can be obtained. The combined use of enzyme libraries and chemical manipulations to generate more powerful polymeric variants of already established drugs has never been undertaken previously in Australia. This approach has the capacity to generate hitherto inaccessible classes of therapeutic entities and to provide a new and unique technology platform for the country's biotechnology industry.Read moreRead less
Chemical Synthesis and Biological Evaluation of Analogues of Platencin, a New-generation Antibiotic. The just discovered natural product platencin displays potent and broad spectrum anti-bacterial activity. It may represent the precursor of a new class of drugs to replace current anti-infective agents which are becoming alarmingly less effective as bacterial resistance increases dramatically. For this reason, platencin has been described as a once in a generation discovery. This study will explo ....Chemical Synthesis and Biological Evaluation of Analogues of Platencin, a New-generation Antibiotic. The just discovered natural product platencin displays potent and broad spectrum anti-bacterial activity. It may represent the precursor of a new class of drugs to replace current anti-infective agents which are becoming alarmingly less effective as bacterial resistance increases dramatically. For this reason, platencin has been described as a once in a generation discovery. This study will exploit two sophisticated new synthetic techniques for the purposes of making analogues of platencin that will be screened by the industry partner, Biota, for anti-bacterial properties. New drug candidates capable of treating especially dangerous infections such as methicillin resistant staphyllococcus aureus (MRSA) should thus emerge.Read moreRead less
Chemoenzymatic Routes to Novel Dendritic Architectures Suitable for Pharmaceutical Applications. Dendritic molecules incorporating multiple copies of a particular functional group on their periphery allow for attachment of drug-like molecules at each of these sites. The resulting conjugates often have vastly superior therapeutic properties relative to the original single drug molecule. This phenomenon is now revolutionizing drug design. Developments in this area are limited by the range of dendr ....Chemoenzymatic Routes to Novel Dendritic Architectures Suitable for Pharmaceutical Applications. Dendritic molecules incorporating multiple copies of a particular functional group on their periphery allow for attachment of drug-like molecules at each of these sites. The resulting conjugates often have vastly superior therapeutic properties relative to the original single drug molecule. This phenomenon is now revolutionizing drug design. Developments in this area are limited by the range of dendritic molecules currently available. Thus, lack of variation in the three-dimensional architecture and the functionality available at the periphery of such constructs is a serious deficiency. This proposal seeks to redress this through the application of novel chemoenzymatic methods developed by the applicant.Read moreRead less
The Development of New, Non-steroidal Anti-Asthma Drugs with Novel Modes of Action. Asthma represents one of Australia's most significant chronic disease states. It adversely affects the lives of many hundreds of thousands of citizens and represents a growing problem, especially amongst younger members of the population. The start-up biotech company Cryptopharma has recently identified a family of steroid derivatives that deliver, through a novel mode of action, significant anti-asthma activity ....The Development of New, Non-steroidal Anti-Asthma Drugs with Novel Modes of Action. Asthma represents one of Australia's most significant chronic disease states. It adversely affects the lives of many hundreds of thousands of citizens and represents a growing problem, especially amongst younger members of the population. The start-up biotech company Cryptopharma has recently identified a family of steroid derivatives that deliver, through a novel mode of action, significant anti-asthma activity in in-vivo models. The purpose of the present work is to develop, through comprehensive synthetic organic chemistry and medicinal chemistry-type studies, non-steroidal analogues of Cryptopharma's lead compound that can be used clinically in the treatment of asthma.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
Generation and exploitation of novel fermentation products in the synthesis of biologically active organic compounds with therapeutic potential. Collections of new micro-organisms and their metabolites suitable for use in the synthesis of potential therapeutic agents will be established. The combined application of molecular biological, microbiological and chemical synthesis techniques in a concerted manner in the one location will lead to major new opportunities for Australian industry.
Reactive intermediates and microwave-assisted organic reactions. The use of our chemistry to help develop new, safer, better drugs against schizophrenia is a strong driving force for this research. This relates to the National Research Priority of promoting and maintaining good health, ageing well and productively, and preventative healthcare. Microwave-assisted chemical synthesis will undoubtedly become a very important methodology in the pharmaceutical industry, and our work will help develop ....Reactive intermediates and microwave-assisted organic reactions. The use of our chemistry to help develop new, safer, better drugs against schizophrenia is a strong driving force for this research. This relates to the National Research Priority of promoting and maintaining good health, ageing well and productively, and preventative healthcare. Microwave-assisted chemical synthesis will undoubtedly become a very important methodology in the pharmaceutical industry, and our work will help developing such know-how in Australia and thereby contribute to the Australian economic fabric. Read moreRead less