A5032516247- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Biochemical and Structural Characterization
- Synthesis and Catalytic Reactions
- Synthetic Organic Chemistry Methods
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Catalysis and Immobilization
- Catalytic Cross-Coupling Reactions
- Asymmetric Synthesis and Catalysis
- Catalytic C–H Functionalization Methods
- Innovative Microfluidic and Catalytic Techniques Innovation
- Crystallography and molecular interactions
- Luminescence and Fluorescent Materials
- Supramolecular Chemistry and Complexes
- Radiopharmaceutical Chemistry and Applications
- Peptidase Inhibition and Analysis
- Synthesis and pharmacology of benzodiazepine derivatives
- Microbial Metabolic Engineering and Bioproduction
- Organic Electronics and Photovoltaics
- Lymphatic System and Diseases
- Advanced Synthetic Organic Chemistry
- Myasthenia Gravis and Thymoma
- 3D Printing in Biomedical Research
- Inhalation and Respiratory Drug Delivery
CSIRO Manufacturing
2015-2024
National Oceanography Centre
2024
Health Sciences and Nutrition
2023
University of Oxford
2007-2022
Materials Science & Engineering
2011-2019
Commonwealth Scientific and Industrial Research Organisation
2011-2019
Monash University
2016-2017
University of Florida
2016
The University of Western Australia
2001-2009
Curtin University
2008
Abstract Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated a chitosan/glucose polymer to produce responsive oral nanoformulation. This formulation pH responsive, insoluble in acidic environments and shows increased absorption human duodenum explants Caenorhabditis elegans at neutral pH. The sensitive glucosidase enzymes trigger release. It found that the...
Abstract The enzyme‐mediated site‐specific bioconjugation of a radioactive metal complex to single‐chain antibody using the transpeptidase sortase A is reported. Cage amine sarcophagine ligands that were designed function as substrates for mediated antibodies synthesized and enzymatically conjugated variable fragment. fragment scFv anti‐LIBS targets ligand‐induced binding sites (LIBS) on glycoprotein receptor GPIIb/IIIa, which present activated platelets. immunoconjugates radiolabeled with...
Reaction of imidazolium-linked ortho-cyclophanes with nickel(II) and palladium(II) salts in the presence acetate base led to formation complexes where a metal centre is bound by pair heterocyclic carbenes which themselves are part cyclophane skeleton. These cyclophane–metal have been characterised NMR spectroscopy (for five complexes) X-ray diffraction studies. The highly active as promoters Heck Suzuki couplings, preliminary studies showing reactions turnover numbers approaching 107.
The crystal structure of a cyanine dye rotaxane shows that the cyclodextrin is tightly threaded round polymethine bridge dye; encapsulation dramatically increases kinetic chemical stability radicals formed on oxidation and reduction dye, making it possible to observe radical dication by ESR UV-vis-NIR spectroscopy.
A novel nickel complex in which the center is bonded to two pyridine units and heterocyclic carbene an imidazolium linked meta-cyclophane skeleton has been synthesized structurally characterized. Both parent imidazolium-linked cyclophane undergo H/D exchange reactions D2O solutions.
A range of mercury-imidazolylidene complexes have been prepared by reaction imidazolium-linked cyclophanes with mercury(II) acetate. For based on meta-xylyl groups the mercury are mononuclear and exhibit unprecedented structures in which atom is bound within cyclophane ring, two NHC donors being mutually trans. ortho-xylyl or 2,6-lutidinediyl dinuclear a [Hg(μ-L)2Hg] core, each coordinated one from unit. The structurally characterized. Studies NHC-pyridinophane complex indicated that NHC−Hg...
Abstract Sortase‐mediated protein ligation is a biological covalent conjugation system developed from the enzymatic cell wall display mechanism found in Staphylococcus aureus . This three‐component requires: (i) purified Sortase A (SrtA) enzyme; (ii) substrate containing LPXTG peptide recognition sequence; and (iii) an oligo‐glycine acceptor molecule. We describe cloning of single‐chain antibody sc528, which binds to extracellular domain epidermal growth factor receptor (EGFR), parental...
The synthesis and characterization of a series azolium-linked cyclophanes are reported. consist two azolium groups (17 examples) or three imidazolium (1 example) linked to benzenoid units (benzene, naphthalene, p-xylene, mesitylene, 1,2,3,4- 1,2,4,5-tetramethylbenzene, 2,6-pyridine, p-tert-butylphenol) via methylene groups. Cyclophanes containing ortho-, meta-, para-substitution patterns in the were examined. conformations examined solution by variable-temperature NMR studies solid state...
The advent of nanomedicine requires novel delivery vehicles to actively target their site action. Here, we demonstrate the development lung-targeting drug-loaded liposomes and efficacy, specificity safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug treat lung injuries. steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar (NSSLs). Targeting functionality performed through conjugation surfactant protein A (SPANb)...
The lymphatic system plays a major role in the metastatic dissemination of cancer and has an integral immunity. PEGylation enhances drainage uptake following subcutaneous (sc) administration proteins protein-like polymers, but impact very large (such as antibodies) on pharmacokinetics is unknown. This study therefore aimed to evaluate sc absorption disposition anti-HER2 antibody trastuzumab rats. PEG-trastuzumab was generated via conjugation single 40 kDa PEG-NHS ester trastuzumab. showed...
Abstract Hydrophilic polyanionic conjugated polyrotaxanes are readily synthesized in water by Suzuki coupling, but their high polarity and ionic nature limit the potential applications of these materials. Here, we demonstrate three methods for transforming polar polyelectrolytes into nonpolar lipophilic insulated molecular wires. A water‐soluble polyfluorene‐ alt ‐biphenylene β‐cyclodextrin (CD) polyrotaxane was converted derivatives methylation carboxylic acid groups with diazomethane...
The lymphatic system is a major conduit by which many diseases spread and proliferate. There therefore increasing interest in promoting better drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, can limit the exposure activity of against lymph-resident diseases. This study explored ideal PEGylation strategies maximize biological using trastuzumab Fab′ model. Specifically, was...
Abstract A series of well‐defined polymer–drug conjugates were prepared in order to modify the physical properties a known cytotoxic drug, 7‐ethyl‐10‐hydroxycamptothecin (SN‐38), active metabolite irinotecan (CPT‐11). Reversible addition–fragmentation chain transfer (RAFT) polymerisation was used covalently and site‐specifically append defined N ‐(2‐hydroxypropyl)methacrylamide (HPMA) polymer SN‐38 using graft‐from process. These poly‐HPMA–SN‐38 displayed excellent aqueous solubility...
The functionalization of proteins with different cargo molecules is highly desirable for a broad range applications. However, the reproducible production defined conjugates multiple functionalities significant challenge. Herein, we report dual site-specific labeling an antibody fragment, utilizing orthogonal Sortase A and π-clamp conjugation methods, demonstrate that binding fragment to its target receptor retained after labeling.
This paper describes the synthesis, structural characterization, and solution behavior of some xylyl-linked imidazolium benzimidazolium cyclophanes decorated with alkyl or alkoxy groups. The addition alkyl/alkoxy chains to allows for studies in chlorinated solvents, whereas previous azolium have generally required highly polar solvents. may exist a syn/syn conformation (azolium rings mutually syn, arene syn) syn/anti anti). preferred is significantly affected by (i) binding bromide (ion...
Identification of tumors which over-express Epidermal Growth Factor Receptor (EGFR) is important in selecting patients for anti-EGFR therapies. Enzymatic bioconjugation was used to introduce positron-emitting radionuclides (89Zr, 64Cu) into an antibody fragment Positron Emission Tomography (PET) imaging the same day as injection. A monovalent with high affinity EGFR engineered include a sequence that recognized by transpeptidase sortase A. Two different metal chelators, one 89ZrIV and...
Sortase A-mediated conjugation reactions were performed with a number of different nucleophiles. A peptide-Im7-labelled conjugate was used to image neuronal cells.
There is currently considerable interest in the intensification of biocatalytic processes to reduce cost goods for biocatalytically produced chemicals, including pharmaceuticals and advanced pharmaceutical intermediates. Continuous-flow biocatalysis shows promise as a method process intensification; however, reliance some reactions on use diffusible cofactors (such nicotinamide cofactors) has proven be technical barrier key enzyme classes. This minireview covers attempts overcome this...
Escherichia coli possesses two acyl ornithine aminotransferases, one catabolic (AstC) and the other anabolic (ArgD), that participate in L-arginine metabolism. Although only 58% identical, enzymes have been shown to be functionally interchangeable. Here we purified AstC obtained X-ray crystal structures of apo holo-AstC enzyme complexed with its physiological substrate, succinylornithine. We compare this study those ArgD from Salmonella typhimurium elsewhere, finding several notable...
Interferon α2 is an antiviral/antiproliferative protein that currently used to treat hepatitis C infections and several forms of cancer. Two PEGylated variants interferon (containing 12 40 kDa PEGs) are marketed display longer plasma circulation times than unmodified interferon. With increasing realization the lymphatic system plays important role in extrahepatic replication virus metastatic dissemination cancers, this study sought evaluate PEGylation strategies optimally enhance antiviral...
Carbon-carbon bond formation is one of the most challenging reactions in synthetic organic chemistry, and aldol catalysed by dihydroxyacetone phosphate-dependent aldolases provide a powerful biocatalytic tool for combining C-C with generation two new stereo-centres, access to all four possible stereoisomers compound. Dihydroxyacetone phosphate (DHAP) unstable so provision DHAP DHAP-dependent processes remains complicated. Our research has investigated efficiency several different enzymatic...