A5010727704- Protein Degradation and Inhibitors
- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Mass Spectrometry Techniques and Applications
- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- Prostate Cancer Diagnosis and Treatment
- Click Chemistry and Applications
- Multiple Myeloma Research and Treatments
- Radical Photochemical Reactions
- Synthesis and Catalytic Reactions
- Nicotinic Acetylcholine Receptors Study
- SARS-CoV-2 detection and testing
- Protein Hydrolysis and Bioactive Peptides
- Catalytic C–H Functionalization Methods
- Historical Art and Culture Studies
- vaccines and immunoinformatics approaches
- Bioactive Compounds and Antitumor Agents
- RNA and protein synthesis mechanisms
- Sulfur-Based Synthesis Techniques
- Glycosylation and Glycoproteins Research
- Musicology and Musical Analysis
The University of Sydney
2012-2024
Australian Research Council
2020-2024
Digital Research Alliance of Canada
2024
Cobham Community Hospital
2024
The COVID-19 pandemic, caused by SARS-CoV-2, has led to substantial morbidity, mortality, and disruption globally. Cellular entry of SARS-CoV-2 is mediated the viral spike protein, affinity ligands this surface protein have potential for applications as antivirals diagnostic reagents. Here, we describe selection cyclic peptide receptor binding domain (RBD) from three distinct libraries (in excess a trillion molecules each) mRNA display. We identified six high with dissociation constants (KD)...
Protein cages are a common architectural motif used by living organisms to compartmentalize and control biochemical reactions. While engineered protein have featured in the construction of nanoreactors synthetic organelles, relatively little is known about underlying molecular parameters that govern stability flux through their pores. In this work, we systematically designed 24 variants Thermotoga maritima encapsulin cage, featuring pores different sizes charges. Twelve pore were...
Significant recent advances in structural biology, particularly the field of cryoelectron microscopy, have dramatically expanded our ability to create models proteins and protein complexes. However, many remain refractory these approaches because their low abundance, stability, or-in case complexes-simply not having yet been analyzed. Here, we demonstrate power using cross-linking mass spectrometry (XL-MS) for high-throughput experimental assessment structures This included those produced by...
Cyclic peptide library screening technologies show immense promise for identifying drug leads and chemical probes challenging targets. However, the structural functional diversity encoded within such libraries is largely undefined. We have systematically profiled affinity, selectivity, features of library-derived cyclic peptides selected to recognize three closely related targets: acetyllysine-binding bromodomain proteins BRD2, -3, -4. report affinities as low 100 pM specificities up...
Abstract Herein, we describe the development and application of a novel expressed protein selenoester ligation (EPSL) methodology for one‐pot semi‐synthesis modified proteins. EPSL harnesses rapid kinetics reactions between synthetic selenopeptides aryl selenoesters (generated from intein fusion precursors) followed by in situ chemoselective deselenization to afford target proteins at concentrations that preclude use traditional methods. The utility technology is showcased through efficient...
The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed safeguard against emerging variants future pandemics. We used messenger RNA (mRNA) display under a reprogrammed genetic code find spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Wuhan strain pseudoviruses...
Abstract The importance of modified peptides and proteins for applications in drug discovery, illuminating biological processes at the molecular level, is fueling a demand efficient methods that facilitate precise modification these biomolecules. Herein, we describe development photocatalytic method rapid dimerization site-specific functionalization peptide protein diselenides. This methodology, dubbed diselenide contraction, involves irradiation 450 nm presence an iridium photocatalyst...
Screening is not recommended for prostate cancer in the UK. Asymptomatic men aged ≥50 years can request a prostate-specific antigen (PSA) test following counselling on potential harms and benefits. There are areas of clinical uncertainty among GPs, resulting content quality varying.
A photoredox-catalyzed method for the indirect generation of acyl radicals from stable thioesters is described.
Abstract Protein cages are a common architectural motif used by living organisms to compartmentalize and control biochemical reactions. While engineered protein have recently been featured in the construction of nanoreactors synthetic organelles, relatively little is known about underlying molecular parameters that govern cage stability flux through their pores. In this work, we systematically designed 24-member library variants based on T. maritima encapsulin, each featuring pores different...
An enantioselective synthesis of the phenyl ring-containing strioglactone, (−)-solanocol, is described.
Abstract Herein, we describe the development and application of a novel expressed protein selenoester ligation (EPSL) methodology for one‐pot semi‐synthesis modified proteins. EPSL harnesses rapid kinetics reactions between synthetic selenopeptides aryl selenoesters (generated from intein fusion precursors) followed by in situ chemoselective deselenization to afford target proteins at concentrations that preclude use traditional methods. The utility technology is showcased through efficient...
ABSTRACT Bromodomains regulate gene expression by recognizing protein motifs containing acetyllysine. Although originally characterized as histone-binding proteins, it has since become clear that these domains interact with other acetylated perhaps most prominently transcription factors. The likely transient nature and low stoichiometry of such modifications, however, made challenging to fully define the interactome any given bromodomain. To begin address this knowledge gap in an unbiased...
Bromodomains (BDs) regulate gene expression by recognizing protein motifs containing acetyllysine. Although originally characterized as histone-binding proteins, it has since become clear that these domains interact with other acetylated perhaps most prominently transcription factors. The likely transient nature and low stoichiometry of such modifications, however, made challenging to fully define the interactome any given BD. To begin address this knowledge gap in an unbiased manner, we...
ABSTRACT Significant recent advances in structural biology, particularly the field of cryo-electron microscopy, have dramatically expanded our ability to create models proteins and protein complexes. However, many remain refractory these approaches because their low abundance, stability or – case complexes simply not having yet been analysed. Here, we demonstrate power combining cross-linking mass spectrometry (XL-MS) with artificial intelligence-based structure prediction discover...
The development of novel antivirals is crucial not only for managing current COVID-19 infections but addressing potential future zoonotic outbreaks. SARS-CoV-2 main protease (M
Abstract The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed safeguard against emerging variants future pandemics. We used mRNA display under a reprogrammed genetic code find spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 Wuhan strain pseudoviruses containing spike proteins or related sarbecoviruses....