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
The molecular basis for oocyst and cyst wall formation in apicomplexan parasites. Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals ....The molecular basis for oocyst and cyst wall formation in apicomplexan parasites. Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals and attack by the immune system. We will discover and characterise the molecular basis for cyst wall formation. This fundamental knowledge will be the building block for new, highly specific drugs and vaccines to control these extremely important pathogens.Read moreRead less
New Methods for Directed Molecular Evolution of Novel Protein Functions. Novel ribosome-based techniques can be used to carry out test-tube evolution of proteins with new structures and functions. The methods rely on (a) physical association of individual nucleic acid molecules with the particular protein molecules they encode, (b) selection of proteins with new functions, and (c) recovery of the attached genetic code. This project will address several issues that currently limit use of these fr ....New Methods for Directed Molecular Evolution of Novel Protein Functions. Novel ribosome-based techniques can be used to carry out test-tube evolution of proteins with new structures and functions. The methods rely on (a) physical association of individual nucleic acid molecules with the particular protein molecules they encode, (b) selection of proteins with new functions, and (c) recovery of the attached genetic code. This project will address several issues that currently limit use of these frontier technologies for evolution of new protein products that have a wide range of practical applications.Read moreRead less
Testing co-evolutionary processes driving venom diversity in tiger snakes. Testing co-evolutionary processes driving venom diversity in tiger snakes. This project aims to examine the geographic variation amongst tiger snakes in anatomy, ecology, and life history traits, and the relationship of these factors to venom toxins and production; and to evaluate the true pharmacological potential of tiger snake venom. This project will investigate the role of venom adaptation in long-term animal evoluti ....Testing co-evolutionary processes driving venom diversity in tiger snakes. Testing co-evolutionary processes driving venom diversity in tiger snakes. This project aims to examine the geographic variation amongst tiger snakes in anatomy, ecology, and life history traits, and the relationship of these factors to venom toxins and production; and to evaluate the true pharmacological potential of tiger snake venom. This project will investigate the role of venom adaptation in long-term animal evolution, by identifying rare venom transcripts involved in providing evolutionary potential for adaptation to environmental change. This is essential as continuing climatic and human-induced alteration of our environment affects southern Australia where many people live, work and interact with native wildlife. Anticipated outcomes are maximizing venom harvests and enhanced snakebite treatment capacity.Read moreRead less