A5042683188- Chemical Synthesis and Analysis
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Click Chemistry and Applications
- Enzyme Structure and Function
- Prostate Cancer Treatment and Research
- Peptidase Inhibition and Analysis
- Receptor Mechanisms and Signaling
- Silk-based biomaterials and applications
- Biochemical and Structural Characterization
- Ubiquitin and proteasome pathways
- Advanced Fluorescence Microscopy Techniques
- Orbital Angular Momentum in Optics
- Organic Chemistry Cycloaddition Reactions
- Advanced Proteomics Techniques and Applications
- Genomics and Chromatin Dynamics
- Antimicrobial Peptides and Activities
- Protease and Inhibitor Mechanisms
- Protein Structure and Dynamics
- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Medical Imaging Techniques and Applications
University of Auckland
2023-2024
Maurice Wilkins Centre
2023-2024
The University of Adelaide
2019-2023
Australian Research Council
2021-2023
ARC Centre for Nanoscale BioPhotonics
2021-2023
RMIT University
2021
Inverse agonists of peroxisome proliferator activated receptor γ (PPARγ) have emerged as safer alternatives to full for their reduced side effects while still maintaining impressive insulin-sensitizing properties. To shed light on molecular mechanism, we characterized the interaction PPARγ ligand binding domain with SR10221. X-ray crystallography revealed a novel mode SR10221 in presence transcriptionally repressing corepressor peptide, resulting much greater destabilization activation...
Abstract Introduction: 177Lu-PSMA-617 is the first FDA-approved targeted radioligand therapy (RLT), and in clinical trials, significantly prolonged survival improved quality of life patients with metastatic castration resistant prostate cancer (mCRPC). However, approximately 30% do not respond to treatment most initial responders ultimately relapse. Compared beta-emitter 177Lu, alpha isotope 212Pb may prove be advantageous due its short half-life, high linear energy transfer, efficient...
Abstract Introduction: PSMA-targeted radioligand therapy (RLT) with lutetium-177 (177Lu), a beta-emitter, has been clinically proven to be efficacious for the treatment of prostate cancer (PC). Although emerging clinical data indicate that better efficacy can achieved by alpha-emitters, toxicities associated actinium-225 (225Ac) may limit its broad application especially in early lines treatment. Lead-212 (212Pb), is promising isotope alpha high linear energy transfer, half-life 10.6 hours,...
The brevicidines represent a novel class of nonribosomal antimicrobial peptides that possess remarkable potency and selectivity toward highly problematic resistant Gram-negative pathogenic bacteria. A recently discovered member the brevicidine family, coined B (2), comprises single amino acid substitution (from d-Tyr2 to d-Phe2) in sequence linear moiety (1) was reported exhibit broader activity against both (MIC = 2–4 μgmL–1) Gram-positive 2–8 pathogens. Encouraged by this, we herein report...
The human sliding clamp, Proliferating Cell Nuclear Antigen (hPCNA), interacts with over 200 proteins through a conserved binding motif, the PIP-box, to orchestrate DNA replication and repair. It is not clear how changes features of PIP-box modulate protein thus they fine-tune downstream processes. Here, we present systematic study each position within reveal hPCNA-interacting peptides bind drastically varied affinities. We synthesized series 27 derived from native p21 small modifications...
Enzymes involved in Staphylococcus aureus amino acid metabolism have recently gained traction as promising targets for the development of new antibiotics, however, not all aspects this process are understood. The ATP-grasp superfamily includes enzymes that predominantly catalyze ATP-dependent ligation various carboxylate and amine substrates. One subset, ʟ-amino ligases (LALs), primarily formation dipeptide products Gram-positive bacteria, their involvement S. has been investigated. Here, we...
Abstract The thiol‐selective fluorescent imaging agent, dibromobimane, has been repurposed to crosslink cysteine‐ and homocysteine‐containing peptides, with the resulting bimane linker acting as both a structural constraint tag. Macrocyclisation was conducted on nine short peptides containing two cysteines and/or homocysteines, on‐resin in buffered aqueous solution, give macrocycles ranging size from 16 ( i , +2) 31 +7) atoms. structures were defined by CD, NMR structure calculations using...
Abstract A new fiber functionalization architecture for single‐fiber imaging and sensing is presented. 5(6)Carboxy‐seminaphthorhodafluor‐2 (a fluorescent pH sensor) attached to a silk‐binding peptide the complex added aqueous silk fibroin protein. These bind with K d of 36 µM as determined by fluorescence polarization assay. The dip‐coated into mixture, scanning electron microscopy images reveal uniform coating on tip. stable repeated washes does not affect light emitted from fiber, which...
The variables effecting successful depsipeptide (ester) bond formation, on-resin, are prioritised to provide a useful troubleshooting guide for synthesis.
An i-i+4 or i-i+3 bimane-containing linker was introduced into a peptide known to target Estrogen Receptor alpha (ERα), in order stabilise an α-helical geometry. These macrocycles were studied by CD and NMR reveal the constrained adopts 310 -helical structure solution, conformation on interaction with ERα coactivator recruitment surface silico. acyclic bimane-modified is also helical, when it includes tryptophan tyrosine residue; but significantly less helical phenylalanine alanine residue,...
The human sliding clamp protein known as proliferating cell nuclear antigen (PCNA) orchestrates DNA-replication and -repair such is an ideal therapeutic target for proliferative diseases, including cancer. Peptides derived from the p21 bind PCNA with high affinity via a 310-helical binding conformation are to shut down DNA-replication. Here, we present studies on short analogues of peptides (143-151) conformationally constrained covalent linker between i, i + 4 separated cysteine residues at...
We present a new coating procedure to prepare optical fibre sensors suitable for use with protein analytes. demonstrate this through the detection of AlexaFluor-532 tagged streptavidin by its binding D-biotin that is functionalised onto an fibre, via incorporation in silk fibroin coating. The was covalently attached silk-binding peptide provide SBP-biotin, which adheres silk-coated tip. These probes were prepared two methods. first involves dip-coating tip into mixture and distributes...
Keywords: peptide, stapled constrained peptidomimetic, fluorescence, helical structure, bimane, secondary structure.
Human proliferating cell nuclear antigen (PCNA) is a critical mediator of DNA replication and repair, acting as docking platform for proteins. Disrupting these interactions with peptidomimetic agent presents promising avenue to limit proliferation cancerous cells. Here, p21-derived peptide was employed starting scaffold design modular that interacts PCNA cellular permeable. Ultimately, produced which met criteria, consisting fluorescein tag SV40 localization signal conjugated the N-terminus...
Invasive fungal infections (IFIs) are prevalent in immunocompromised patients. Due to alarming levels of increasing resistance clinical settings, new drugs targeting the major pathogen Aspergillus fumigatus required. Attractive drug targets those involved essential processes like DNA replication, such as proliferating cell nuclear antigens (PCNAs). PCNA has been previously studied cancer research and presents a viable target for antifungals. Human interacts with p21 protein, outcompeting...
A single-fiber-based probe with a diameter of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\boldsymbol{125 \mu \mathrm{m}}$</tex> , capable combined imaging and sensing, was developed applied in an vitro fertilization setting. The can resolve cumulus oocyte complex within ovarian follicle, measure pH change 0.04 units.