Towards The Rational Design Of Calcium Sensing Receptor Allosteric Modulators For The Treatment Of Osteoporosis And Calcium Handling Disorders
Funder
National Health and Medical Research Council
Funding Amount
$741,390.00
Summary
Drugs that target the human calcium sensing receptor can be too strong or too weak, resulting in side effects or lack of efficacy. This proposal thus seeks to establish whether the strength of drug activity can be rationally altered and exploited to treat different disease states by fine-tuning CaSR activity in a disease-specific manner.
New Positive Allosteric Modulators Of Nicotinic Acetylcholine Receptors For Treatment Of Cognitive Impairment In ADHD
Funder
National Health and Medical Research Council
Funding Amount
$612,851.00
Summary
The effects of Attention Deficit Hyperactivity Disorder (ADHD) can extend well beyond childhood. This project will target the nicotinic acetylcholine receptor family for developing new therapeutics to manage this disease.
Molecular Interactions Of Novel Conotoxin Inhibitors Of The Noradrenaline Transporter
Funder
National Health and Medical Research Council
Funding Amount
$392,036.00
Summary
A novel class of conotoxins (chi-conotoxins) has been discovered in the venom of an Australian cone snails, Conus marmoreus. Chi-conotoxins are the first peptide inhibitors of the noradrenaline transporter. From binding studies, it appears they act at a new site, remote from the site of action of antidepressants. This project is aimed at understanding how and where this novel class of peptide binds to the transporter. The results of this study are designed to maximise the potential of these pate ....A novel class of conotoxins (chi-conotoxins) has been discovered in the venom of an Australian cone snails, Conus marmoreus. Chi-conotoxins are the first peptide inhibitors of the noradrenaline transporter. From binding studies, it appears they act at a new site, remote from the site of action of antidepressants. This project is aimed at understanding how and where this novel class of peptide binds to the transporter. The results of this study are designed to maximise the potential of these patented peptides to be used as leads to the development of a new class of therapeutic for controlling the adverse effects of inadequate noradrenaline balance.Read moreRead less
Developing Novel Selective Glycine Receptor Potentiators As A Means To Control Pain.
Funder
National Health and Medical Research Council
Funding Amount
$552,647.00
Summary
It has been estimated that >3M Australians suffer from pain at a cost to the economy of >$34B, with chronic pain (persisting beyond 1-6 mths) accounting for ~half this burden. There is an urgent and compelling social and economic case for the development of safer and more effective pain therapeutics. This project takes inspiration from a new class of Australian marine natural products that selectively regulate a key pain pathway, and will optimize and develop these as a new class of pain d ....It has been estimated that >3M Australians suffer from pain at a cost to the economy of >$34B, with chronic pain (persisting beyond 1-6 mths) accounting for ~half this burden. There is an urgent and compelling social and economic case for the development of safer and more effective pain therapeutics. This project takes inspiration from a new class of Australian marine natural products that selectively regulate a key pain pathway, and will optimize and develop these as a new class of pain drug.Read moreRead less
Bismuth Compounds And Materials As Antibacterial Agents
Funder
National Health and Medical Research Council
Funding Amount
$476,535.00
Summary
Antimicrobial resistance has been identified by the World Health Organisation as one of the greatest threats we face globally. The amount of effective antibacterial agents is rapidly diminishing. The threat of antimicrobial resistance is greatest in hospitals and health-care facilities. Our project aims to produce a new range of bismuth based antibacterial materials, which will be used in devices, coatings and surfaces in the clinic, to combat the rise of infections caused by resistant bacteria.
Development Of Peptide-based Scaffolds For Intracellular Cancer Targets
Funder
National Health and Medical Research Council
Funding Amount
$1,479,836.00
Summary
The overall aim of this project is to develop peptide-based drugs that are able to cross cell membranes and inhibit specific targets inside cells leading to more effective, safer and cost effective drugs for cancer. One potential outcome of the project will be new drug leads to treat melanoma and leukemia that are likely to be less toxic, more potent and less likely to develop resistance than current treatments.
Structure-based Design Of Inhibitors Of PimA - A New Target For Tuberculosis Therapy
Funder
National Health and Medical Research Council
Funding Amount
$666,246.00
Summary
Tuberculosis (TB) is a devastating disease that kills 2 million people worldwide each year and affects one-third of the entire human population. Bacterial resistance to existing antibiotics is an ever increasing problem, highlighting the need to develop new anti-TB drugs. The aim of this project is to develop specific inhibitors to target a protein that is essential for the survival of the tuberculosis bacterium.
The Structural Basis Of The Interaction Of Human Relaxins With Their Receptors.
Funder
National Health and Medical Research Council
Funding Amount
$489,000.00
Summary
Human Gene 2 (H2) relaxin is a peptide hormone structurally related to insulin and has numerous biological actions related to its roles during pregnancy. It exerts these primarily by inducing the breakdown of collagen and the formation of new blood vessels while simultaneously stimulating tissue growth and inhibiting cell death. Its functions have led to several potential therapeutic roles for relaxin being explored. These include the treatment of fibrotic disorders and peripheral vascular disea ....Human Gene 2 (H2) relaxin is a peptide hormone structurally related to insulin and has numerous biological actions related to its roles during pregnancy. It exerts these primarily by inducing the breakdown of collagen and the formation of new blood vessels while simultaneously stimulating tissue growth and inhibiting cell death. Its functions have led to several potential therapeutic roles for relaxin being explored. These include the treatment of fibrotic disorders and peripheral vascular disease. H2 relaxin is the principal expression product in vivo and has been shown to exert a wide range of physiological responses beyond those normally associated with pregnancy. We have recently discovered another human - H3 - relaxin that is expressed primarily in the brain which strongly suggests a neuropeptide role. Surprisingly, H2 and 3 relaxins each act via different G-protein coupled receptors. We will perform detailed structure-function studies to determine how these relaxins impart their specific biological actions. Modern chemical synthesis protocols will be used to prepare each of these complex peptides in adequate quantities for detailed secondary and tertiary structural study. Analogues containing modified residues and global domains will be prepared and assayed for characteristic relaxin agonist and antagonist activity. Sophisticated biomolecular interaction analyses will be used to identify differences in receptor binding regions for the two relaxins. The results, together with those obtained by three-dimensional structural analysis using NMR spectroscopy, will allow us to ultimately define the key features of the H2 and 3 hormones that are responsible for selective receptor binding and specific relaxin activity. We will then be able to design smaller, more stable, orally active relaxin mimetics. Such compounds will have great potential for therapeutic application in the treatment of fibrosis or as biological and pharmacological probes of relaxin action.Read moreRead less