A5073679655- Chemical Synthesis and Analysis
- Dendrimers and Hyperbranched Polymers
- Synthesis and Biological Evaluation
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Adipokines, Inflammation, and Metabolic Diseases
- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Reactions
- Influenza Virus Research Studies
- Metabolism, Diabetes, and Cancer
- RNA and protein synthesis mechanisms
- Organometallic Complex Synthesis and Catalysis
- Cancer Treatment and Pharmacology
- Neurological diseases and metabolism
- Inflammasome and immune disorders
- Monoclonal and Polyclonal Antibodies Research
- Advanced Polymer Synthesis and Characterization
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Synthetic Organic Chemistry Methods
- Atherosclerosis and Cardiovascular Diseases
- Synthesis and characterization of novel inorganic/organometallic compounds
- Cardiac and Coronary Surgery Techniques
- Organoboron and organosilicon chemistry
- Cyclopropane Reaction Mechanisms
Baker Heart and Diabetes Institute
2012-2025
The University of Melbourne
2011-2021
CSIRO Manufacturing
2014
Beth Israel Deaconess Medical Center
2011
Harvard University
2011
St Vincents Institute of Medical Research
2011
Emory University
2011
Starpharma (Australia)
2003-2010
Monash University
2000-2009
Monash Institute of Medical Research
2009
The impact of PEGylation on the pharmacokinetics and biodistribution (3)H-labeled poly l-lysine dendrimers has been investigated after intravenous administration to rats. volumes distribution, clearance consequently plasma half-lives PEGylated were markedly dependent total molecular weight dendrimer, but not specifically affected by PEG chain length alone. In general, larger dendrimer constructs (i.e. >30 kDa) had reduced poorly renally cleared exhibited extended elimination ( t 1/2 1-3...
Background Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers highly branched nanoparticles being developed as microbicides. However, anti-HIV HSV structure-activity relationship dendrimers comprising benzyhydryl amide cores lysine branches, a comprehensive analysis their broad-spectrum activity mechanism action have not been published. Methods Findings with optimized against HIV-1 HSV-2 were...
Dendrimers have potential for delivering chemotherapeutic drugs to solid tumors via the enhanced permeation and retention (EPR) effect. The impact of conjugation hydrophobic anticancer hydrophilic PEGylated dendrimer surfaces, however, has not been fully investigated. current study therefore characterized effect on disposition conjugating alpha-carboxyl protected methotrexate (MTX) a series (3)H-labeled poly-l-lysine dendrimers ranging in size from generation 3 (G3) 5 (G5) rats. contained...
AimsElevated serum C-reactive protein (CRP) following myocardial infarction (MI) is associated with poor outcomes. Although animal studies have indicated a direct pathogenic role of CRP, the mechanism underlying this remains elusive. Dissociation pentameric CRP (pCRP) into pro-inflammatory monomers (mCRP) may directly link to inflammation. We investigated whether cellular microparticles (MPs) can convert pCRP mCRP and transport MI.
Cationic poly-L-lysine 3H-dendrimers with either 16 or 32 surface amine groups (BHALys [Lys]4 [3H-Lys]8 [NH2]16 and BHALys [Lys]8 [3H-Lys]16 [NH2]32, generation 3 4, respectively) have been synthesized their pharmacokinetics biodistribution investigated after intravenous administration to rats. The species in plasma which radiolabel was associated also by size exclusion chromatography (SEC). Rapid initial removal of from evident for both dendrimers (t(1/2) < 5 min). Approximately 1 h...
Article5 December 2022Open Access Source DataTransparent process A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein Johannes Zeller orcid.org/0000-0002-8122-9063 Department of Plastic and Hand Surgery, University Freiburg Medical Centre, Faculty the Freiburg, Germany Baker Heart Diabetes Institute, Melbourne, Vic., Australia Contribution: Conceptualization, Data curation, Formal analysis, Supervision, Validation, Investigation,...
Background Staphylococcus aureus (S. aureus) is a common pathogen capable of causing life-threatening infections. Staphylococcal superantigen-like protein 5 (SSL5) has recently been shown to bind platelet glycoproteins and induce activation. This study investigates further the interaction between SSL5 glycoproteins. Moreover, using glycan discovery approach, we aim identify potential glycans therapeutically target this prevent SSL5-induced effects. Methodology/Principal Findings In addition...
Although part of the coenzyme A pathway, vanin 1 (also known as pantetheinase) sits on cell surface many types an ectoenzyme, catalyzing breakdown pantetheine to pantothenic acid (vitamin B 5 ) and cysteamine, a strong reducing agent. Vanin was initially discovered protein involved in homing leukocytes thymus. Numerous studies have shown that is inflammation, more recent key role metabolic disease. Here, X-ray crystal structure human at 2.25 Å resolution presented, which first reported from...
<title>Abstract</title> CD14 is a widely validated marker for monocyte/macrophage activity as well an inflammatory biomarker and upstream regulator of macrophage activity. We herein test the hypothesis that interventional blockade with murine analogue atibuclimab, anti-CD14 antibody, which has recently been reported to have favorable safety profile, prevents secondary immunological exacerbation cardiac injury in translational mouse model reperfused ST-elevation myocardial infarction (STEMI)...
Respiratory infections caused by human rhinovirus are responsible for severe exacerbations of underlying clinical conditions such as asthma in addition to their economic cost terms lost working days due illness. While several antiviral compounds treating rhinoviral have been discovered, none succeeded, date, reaching approval use. We developed a potent, orally available inhibitor 6 that has progressed through early trials. The compound shows favorable pharmacokinetic and activity profiles...
Sweet medicine: Glycosylated analogues of pramlintide, in which specific Asn residues bear extended N-glycan structures, may be accessed by a combination solid-phase peptide synthesis and highly efficient enzymatic glycosylation (see scheme; ENGases=endo-β-N-acetylglucosaminidases). Glycopeptides display both vitro vivo activity as amylin receptor agonists effect 'smoothing' blood glucose. As service to our authors readers, this journal provides supporting information supplied the authors....
Abstract A unique two‐step modular system for site‐specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase incorporation strained cyclooctyne functional groups. second involves azide–alkyne cycloaddition click reaction. versatility has been exemplified by selective fluorescent dyes a positron‐emitting copper‐64 radiotracer fluorescence positron‐emission tomography imaging activated platelets,...
Tritium-labeled poly-l-lysine dendrimers displaying 8 or 16 surface lysines have been capped with benzene sulfonate (BS), disulfonate (BDS), succinate (Succ) groups, and the intravenous pharmacokinetics disposition profiles of resulting (Lys8(BS)16, Lys16(BS)32, Lys16(BDS)32, Lys16(Succ)32) evaluated. Lys16(Succ)32 was rapidly removed from plasma primarily via renal elimination. Lys16(BS)32 Lys16(BDS)32 were opsonized, in more prolonged elimination kinetics increased uptake by liver. Data...
We have used atomistic molecular dynamics simulations to study the molecular-scale structure of poly(l-lysine) dendrimers homogeneously functionalized with naphthalene disulfonate caps from first generation sixth generation. These behave as typical in poor solvent. As number increases, there is a change small molecule behavior more polymer-like behavior. The first- and second-generation dendrimers, behaving molecules, are flexible, aspherical, exposed environment, their cluster together....
Seleno-organic glutathione peroxidase (GPx) mimetics, including ebselen (Eb), have been tested in vitro studies for their ability to scavenge reactive oxygen and nitrogen species, hydrogen peroxide peroxynitrite. In this study, we investigated the efficacies of two Eb analogues, m-hydroxy (ME) ethanol-ebselen (EtE) compared these with cell based assays. We found that ME is superior attenuating activation peroxide-induced pro-inflammatory mediators, ERK P38 human aortic endothelial cells....
A series of capsid-binding compounds was screened against human rhinovirus (HRV) using a CPE based assay. The ethyl oxime ether 14 found to have outstanding anti-HRV activity (median IC(50) 4.75 ng/mL), and unlike the equivalent ester compound 3 (Pirodavir), it has good oral bioavailability, making promising development candidate. Compound illustrates that an group can act as metabolically stable bioisostere for functionality.
Insulin resistance is a heterogeneous disorder caused by range of genetic and environmental factors, we hypothesize that its etiology varies considerably between individuals. This heterogeneity provides significant challenges to the development effective therapeutic regimes for long-term management type 2 diabetes. We describe novel strategy, using large-scale gene expression profiling, develop signature (GES) reflects overall state insulin in cells patients. The GES was developed from...
We previously used Gene Expression Signature technology to identify methazolamide (MTZ) and related compounds with insulin sensitizing activity in vitro. The effects of these were investigated diabetic db/db mice, insulin-resistant diet-induced obese (DIO) rats streptozotocin (STZ)-induced diabetes. MTZ reduced fasting blood glucose HbA(1c) levels improved tolerance DIO enhanced the glucose-lowering exogenous administration STZ-induced Hyperinsulinemic-euglycemic clamps mice revealed that...
Targeting cell division autoantigen 1 (CDA1) is postulated to attenuate the profibrotic actions of transforming growth factor-β in diabetic nephropathy. This study has identified a regulatory protein for CDA1 and then used genetic pharmacological approaches test vivo whether strategies target this pathway would lead reduced renal injury. A novel protein, named CDA1BP1 (CDA1 binding 1), was as critical regulating activity CDA1. Genetic deletion attenuated key parameters fibrosis mice....