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
Synthetic, Molecular and Biological Studies on Novel Marine Metabolites Isolated from Great Barrier Reef Sponges. Whilst structurally remarkable marine natural products, generated via unprecedented biosynthetic pathways, continue to be isolated from organisms found on the Barrier Reef these substances remain largely unexploited in terms of both their potent biological and ecological properties. Efficient syntheses of two classes of marine metabolites will be undertaken to allow biological, biosy ....Synthetic, Molecular and Biological Studies on Novel Marine Metabolites Isolated from Great Barrier Reef Sponges. Whilst structurally remarkable marine natural products, generated via unprecedented biosynthetic pathways, continue to be isolated from organisms found on the Barrier Reef these substances remain largely unexploited in terms of both their potent biological and ecological properties. Efficient syntheses of two classes of marine metabolites will be undertaken to allow biological, biosynthetic and ecological evaluation of advanced intermediates and final products. Such evaluations will provide new insights into the therapeutic and ecological potential as well as the origins of these natural products. New agents for the management of marine ecosystems and the treatment of oncological and other diseases should emerge.Read moreRead less
Total Synthesis and Biological Evaluation of Australian Sponge Metabolites. The development of functional syntheses of Australian natural products and certain analogues of ecological and therapeutic significance will emerge. Such activities will lead to the identification and evaluation of molecular entities of value in managing marine environments, reduce the need for removal of organisms from marine environments both within and outside of Australia as well as helping maintain and enhance chemi ....Total Synthesis and Biological Evaluation of Australian Sponge Metabolites. The development of functional syntheses of Australian natural products and certain analogues of ecological and therapeutic significance will emerge. Such activities will lead to the identification and evaluation of molecular entities of value in managing marine environments, reduce the need for removal of organisms from marine environments both within and outside of Australia as well as helping maintain and enhance chemical synthesis capacity within the country. The proposed studies could lead to the identification of related natural products produced by organisms on the Great Barrier Reef and that may display even more potent activities and/or complementary ecological roles.Read moreRead less