Design And Delivery Of Peptide-based Anti-cancer Grb7 Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$603,126.00
Summary
The Grb7 protein is overproduced in many types of cancer cells and plays a role in cancer cell growth and spread. The current proposal builds upon the discovery of a peptide-based Grb7 inhibitor that has anti-cancer activity. This proposal is to prepare more potent inhibitor molecules that can efficiently reach the target cancer cells. Such molecules will be used for the study of Grb7 and for the development of a new Grb7-based anti-cancer drug therapy.
This project will unleash the potential of peptide drugs by overcoming their final barrier to widespread use, their synthesis. Plants naturally produce ultra-stable cyclic peptides. We will co-opt their machinery to produce in seeds, two drug leads that have potential as treatments for prostate cancer and chronic neuropathic pain. As an �organic� drug source, seeds have the potential to improve patient compliance and low-tech production systems will allow technology transfer to third-world natio ....This project will unleash the potential of peptide drugs by overcoming their final barrier to widespread use, their synthesis. Plants naturally produce ultra-stable cyclic peptides. We will co-opt their machinery to produce in seeds, two drug leads that have potential as treatments for prostate cancer and chronic neuropathic pain. As an �organic� drug source, seeds have the potential to improve patient compliance and low-tech production systems will allow technology transfer to third-world nations.Read moreRead less
Development Of Next Generation Drugs For Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$632,726.00
Summary
Chronic myeloid leukaemia (CML) is one of the four most common types of leukaemia. With current therapies, 15–20% of patients newly diagnosed for CML will die in the next five years, and it is therefore vitally important to discover new treatments. The aim of this project is to develop a new generation of drugs to treat CML based on new approaches (i.e., different type of molecules and different binding site) that can combat the resistance acquired to the current treatments.
Mimicking Protein Surfaces With Cyclic Peptides: W-conotoxin GVIA Mimics As Novel Analgesic And Neuroprotective Agents
Funder
National Health and Medical Research Council
Funding Amount
$216,412.00
Summary
The omega-conotoxins are small polypeptides (of around 25 residues) cross-linked by three disulfide bonds. At least two of these, omega-conotoxins GVIA and MVIIA, are potent and selective blockers of N-type voltage-gated calcium channels. Administered to the CNS via an intrathecal catheter, MVIIA and GVIA are analgesic in acute, chronic and neuropathic pain models, and protective following ischaemia-induced neuronal injury, such as occurs following stroke. They do not suffer from the development ....The omega-conotoxins are small polypeptides (of around 25 residues) cross-linked by three disulfide bonds. At least two of these, omega-conotoxins GVIA and MVIIA, are potent and selective blockers of N-type voltage-gated calcium channels. Administered to the CNS via an intrathecal catheter, MVIIA and GVIA are analgesic in acute, chronic and neuropathic pain models, and protective following ischaemia-induced neuronal injury, such as occurs following stroke. They do not suffer from the development of tolerance, in contrast with the opioids, such as morphine, which lose their analgesic potency over time and have undesirable side effects. We have determined the three-dimensional structure of GVIA and mapped onto that structure its calcium channel binding surface. This information is a starting point for the structure-based design of truncated and stabilised peptidic analogues of GVIA, which should have several advantages over the native polypeptides as candidates for the treatment of chronic pain and ischaemia-induced neuronal damage. In the course of this work we shall also generate a range of libraries of experimentally determined and predicted structures based on small, cyclic peptides. These libraries will be valuable tools for mimicking key functional regions of protein surfaces in small molecules that are easily (and cheaply) synthesised and have potentially favourable bioavailability. Thus, this project will also increase our understanding of the attributes of small cyclic peptides as mimics of functionally important protein surfaces and provide valuable tools for the design and evaluation of such peptides.Read moreRead less
Developing Species-specific, Structure-targeting Peptides As A Novel Class Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$607,967.00
Summary
Multidrug, antibiotic resistance is a serious global threat. It is a real possibility that in the absence of new antibiotics, common infections could soon become untreatable. This project will develop a novel class of antibiotics that target the core structures of essential bacterial proteins. The successful outcome of this work will also aid the development of specific peptide-based inhibitors for numerous additional diseases, including viral and fungal infections and cancer.
Further Development Of The Clinical Potential Of H2 Relaxin
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
The hormone relaxin mediates cardiovascular and kidney changes during pregnancy. These important functions have led to its current use in clinical trials for the treatment of acute heart failure, a condition affecting millions of patients worldwide. However, there is an urgent need for a longer lasting form of relaxin for prolonged treatment of patients. Our studies will focus on understanding the blood breakdown of the peptide to lead to the design of longer lasting relaxin analogues.