A5052222929- Biochemical and Molecular Research
- Weed Control and Herbicide Applications
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Synthesis and Catalytic Reactions
- Plant tissue culture and regeneration
- Malaria Research and Control
- Phosphodiesterase function and regulation
- Carbohydrate Chemistry and Synthesis
- Synthesis and Biological Evaluation
- Polyamine Metabolism and Applications
- Insect Resistance and Genetics
- Synthesis and biological activity
- Microbial Natural Products and Biosynthesis
- Trypanosoma species research and implications
- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
- Mast cells and histamine
- Neurogenetic and Muscular Disorders Research
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Parkinson's Disease Mechanisms and Treatments
- Quinazolinone synthesis and applications
La Trobe University
2013-2023
Institute for Molecular Science
2016-2019
Monash University
2004-2005
Box Hill Hospital
2004-2005
Abstract Mitochondrial dynamin-related protein 1 (Drp1) is a large GTPase regulator of mitochondrial dynamics and known to play an important role in numerous pathophysiological processes. Despite being the most widely used Drp1 inhibitor, specificity Mdivi-1 towards human has not been definitively proven there have issues reported with its use including off-target effects. In our hands showed varying binding affinities toward Drp1, potentially impacted by compound aggregation. Herein, we...
Dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step in lysine biosynthesis pathway of bacteria. The can be regulated by feedback inhibition DHDPS through allosteric binding end product, lysine. current dogma states that from Gram-negative bacteria are inhibited but orthologs Gram-positive species not. 1.65-Å resolution structure Legionella pneumophila and 1.88-Å Streptococcus pneumoniae bound to lysine, together with comprehensive functional analyses, show this is...
We developed a novel series of antimalarial compounds based on 4-cyano-3-methylisoquinoline. Our lead compound MB14 achieved modest inhibition the growth in vitro human malaria parasite, Plasmodium falciparum. To identify its biological target we selected for parasites resistant to MB14. Genome sequencing revealed that all bore single point S374R mutation sodium (Na+) efflux transporter PfATP4. There are many known inhibit PfATP4 and some under preclinical development. was shown Na+...
A fragment-based drug discovery approach was taken to target the thiol-disulfide oxidoreductase enzyme DsbA from Escherichia coli (EcDsbA). This is critical for correct folding of virulence factors in many pathogenic Gram-negative bacteria, and small molecule inhibitors can potentially be developed as anti-virulence compounds. Biophysical screening a library fragments identified several classes with affinity EcDsbA. One hit high mM affinity, 2-(6-bromobenzofuran-3-yl)acetic acid (6),...
Weeds are becoming increasingly resistant to our current herbicides, posing a significant threat agricultural production. Therefore, new herbicides with novel modes of action urgently needed. In this study, we exploited herbicide target, dihydrodipicolinate synthase (DHDPS), which catalyses the first and rate-limiting step in lysine biosynthesis. The class plant DHDPS inhibitors micromolar potency against Arabidopsis thaliana was identified using high-throughput chemical screen. We...
A series of 4-cyano-3-methylisoquinolines have been shown to inhibit parasite cytokinesis and erythrocyte invasion.
Herbicides with novel modes of action are urgently needed to safeguard global agricultural industries against the damaging effects herbicide-resistant weeds. We recently developed first herbicidal inhibitors lysine biosynthesis, which provided proof-of-concept for a promising herbicide target. In this study, we expanded upon our understanding mode biosynthesis inhibitors. previously postulated that these may act as proherbicides. Here, show is not case. report an additional inhibitors,...
DHDPS represents a novel enzyme target for the development of new antibiotics to combat multidrug resistance.
Prodrugs for PI3K: A series of substituted analogues the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit isolated enzyme but not MCF7 cell proliferation. Two tetrazolyl-substituted further derivatized as prodrugs resulting in restoration cell-based activity. These data provide a conceptual model development tumor-targeting prodrug forms cell-impermeable PI3K inhibitors.
The electronic spectra of 2-bromoethylbenzene and its chloro fluoro analogues have been recorded by resonant two-photon ionisation (R2PI) spectroscopy. Anti gauche conformers assigned rotational band contour analysis IR-UV ion depletion spectroscopy in the CH region. Hydrate clusters anti also observed, allowing role halocarbons as hydrogen bond acceptors to be examined this context. donor OH stretch water bound chlorine is red-shifted 36 cm-1, or 39 cm-1 case bromine. Although classed weak...
A convenient and cost-effective method for the synthesis of Fmoc/Boc-protected peptide nucleic acid monomers is described. The Fmoc/Boc strategy was developed in order to eliminate solubility issues during solid-phase synthesis, particular that cytosine monomer, occurred when using commercialized Bhoc chemistry approach.
To the N-terminus of a nonamer peptide nucleic acid sequence, H-GCACGACTT-NH2, was attached number lipophilic conjugate molecules including three synthetic tocopherol (vitamin E) analogues. Studies were then undertaken with complementary PNA and DNA sequences to explore effects conjugates using techniques UV monitored melting curves isothermal calorimetry. Duplex formation observed when benzopyran group vitamin E conjugated. However, in presence phytyl chain E, binding found be temperature dependent.