A5016035386- Advanced biosensing and bioanalysis techniques
- Click Chemistry and Applications
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Advanced Chemical Physics Studies
- Mast cells and histamine
- RNA Interference and Gene Delivery
- SARS-CoV-2 and COVID-19 Research
- Fiber-reinforced polymer composites
- Receptor Mechanisms and Signaling
- Biochemical and Molecular Research
- Advanced Thermodynamics and Statistical Mechanics
- Synthesis and properties of polymers
- Bacteriophages and microbial interactions
- Protein Structure and Dynamics
- Cancer therapeutics and mechanisms
- Phase Equilibria and Thermodynamics
- Synthesis and biological activity
- Electrochemical Analysis and Applications
- Spectroscopy and Quantum Chemical Studies
- COVID-19 Clinical Research Studies
- Supramolecular Self-Assembly in Materials
- Biosensors and Analytical Detection
- Electrostatics and Colloid Interactions
- Nanoparticle-Based Drug Delivery
McGill University
2019-2025
University of Victoria
2019-2022
SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. necessary not sufficient development clinical disease. Currently, there are no approved pre- or post-exposure prophylactic medical countermeasures. Clinical data suggest that famotidine may mitigate disease, both mechanism action rationale dose selection remain obscure. We have investigated several plausible hypotheses activity including antiviral host-mediated...
Abstract Triggering the release of small molecules in response to unique biomarkers is important for applications drug delivery and biodetection. Due low quantities biomarker, amplifying necessary gain appreciable responses. Nucleic acids have been used both their biomarker‐recognition properties as stimuli, notably amplified small‐molecule by nucleic‐acid‐templated catalysis (NATC). The multiple components reversibility NATC, however, make it difficult apply vivo. Herein, we report use...
Covalent enzyme inhibitors can offer high potency and specificity are increasingly sought after in drug discovery. They typically inhibit two steps: noncovalent binding followed by covalent bond formation. Rational optimization requires quantitative information on both steps. Current methods for measuring these steps technically demanding, time-consuming, not well suited routine insertion into discovery pipelines. We have developed a new approach, using isothermal titration calorimetry...
The complex folding energy landscape of DNA G-quadruplexes leads to numerous conformations for this functionally important class noncanonical structures. A new layer conformational heterogeneity comes from sequences with different numbers G-nucleotides in each the G-strands that form four-stranded G-quartet core. mechanisms by which transition one folded conformation another are currently unknown. To address question, we studied two G-quadruplexes, selecting a single blocking hydrogen...
Abstract SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic medical countermeasures. Clinical data suggest that famotidine may mitigate disease, both mechanism action rationale dose selection remain obscure. We explore several plausible avenues activity including antiviral host-mediated actions. propose the principal involves on-target histamine receptor H 2...
Human chromosomes terminate in long, single-stranded, DNA overhangs of the repetitive sequence (TTAGGG)n. Sets four adjacent TTAGGG repeats can fold into guanine quadruplexes (GQ), four-stranded structures that are implicated telomere maintenance and cell immortalization targets cancer therapy. Isolated GQs have been studied detail, however much less is known about folding long repeat sequences. Such chains adopt an enormous number configurations containing various arrangements unfolded...
G-quadruplex and i-motif nucleic acid structures are believed to fold through kinetic partitioning mechanisms. Such mechanisms explain the structural heterogeneity of metastable intermediates which have been extensively reported. On other hand, folding is regarded as predictable, research on alternative folds limited. While TC5 normally into a stable tetrameric in solution, we report that 2'-deoxy-2'-fluoroarabinocytidine (araF-C) substitutions can prompt form an off-pathway...
Nucleobase mimicking small molecules able to reconfigure DNA are a recently discovered strategy that promises extend the structural and functional diversity of nucleic acids. However, only simple, unfunctionalized such as cyanuric acid melamine have so far been used in this approach. In work, we show addition substituted can successfully program polyadenine strands assemble into supramolecular fibers. Unlike conventional nanostructure functionalization, which typically end-labels strands,...
Abstract G-quadruplexes (G4s) are four-stranded, guanine-rich nucleic acid structures that can influence a variety of biological processes such as the transcription and translation genes DNA replication. In many cases, single G4-forming sequence adopt multiple different folded conformations interconvert on biologically relevant timescales, entropically stabilizing state. The coexistence also suggests there pathways leading from unfolded to state ensembles, potentially modulating folding rate...
Intramolecular guanine quadruplexes (G4s) are non-canonical nucleic acid structures formed by four (G)-rich tracts that assemble into a core of stacked planar tetrads. G4-forming DNA sequences enriched in gene promoters and implicated the control expression. Most contains more G residues than can simultaneously be incorporated resulting variety different possible G4 structures. Although this kind structural polymorphism is well recognized literature, there remain unanswered questions...
Abstract SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic medical countermeasures. Clinical data suggest that famotidine may mitigate disease, both mechanism action rationale dose selection remain obscure. We explore several plausible avenues activity including antiviral host-mediated actions. propose the principal involves on-target histamine receptor H 2...
SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic medical countermeasures. Clinical data suggest that famotidine may mitigate disease, both mechanism action rationale dose selection remain obscure. We explore several plausible avenues activity including antiviral host-mediated actions. propose the principal involves on-target histamine receptor H 2...
Supramolecular chemistry involves the noncovalent assembly of monomers into materials with unique properties and wide-ranging applications. Thermal analysis is a key analytical tool in this field, as it provides quantitative thermodynamic information on both structural stability nature underlying molecular interactions. However, there exist many supramolecular systems whose kinetics are so slow that methods currently applied unreliable or fail completely. We have developed simple rapid...
The nanoscale region immediately adjacent to surfaces, although challenging probe, is directly responsible for local chemical and physical interactions between a material its surroundings. Cell–surface contacts are mediated by combination of electrostatic acid–base that alter the environment over time. In this study, label-free vibrational probe with nanometer length scale reveals potential at silica surface gradually increases in presence bacteria solution. We illustrate cells themselves...
Efficient delivery of therapeutic compounds to their sites action has been a ubiquitous concern throughout the history human medicine. The tumor microenvironment offers variety endogenous stimuli that may be exploited by responsive nanocarrier, including heterogeneities in redox potential. In early stages design such systems, it is necessary develop comprehensive understanding biophysical mechanism which stimulus response occurs, as well how change from inclusion cargo compounds. We describe...
The global emergence of COVID-19, caused by SARS-CoV-2, has underscored the critical need for effective antivirals against coronaviruses. 3-chymotrypsin-like protease (3CLpro) coronavirus been a primary target drug development due to its role across various Following our initial report, this study focuses on structure-based optimization 3CLpro covalent inhibitors. With guidance molecular docking and binding parameters measured from an innovative isothermal titration calorimetry-kinetic...
Papain-like protease (PLpro) and 3-chymotrypsin-like (3CLpro or Mpro) are enzymes essential for the replication of SARS-CoV-2, virus responsible COVID-19. While 3CLpro has been main target many potential antivirals including nirmatrelvir (active ingredient Paxlovid), PLpro proven to be more difficult only a handful inhibitors have disclosed. would highly valuable tools in fight against COVID19 resistant strains future coronavirus pandemics. Combining our experience with covalent expertise...
Abstract Triggering the release of small molecules in response to unique biomarkers is important for applications drug delivery and biodetection. Due low quantities biomarker, amplifying necessary gain appreciable responses. Nucleic acids have been used both their biomarker‐recognition properties as stimuli, notably amplified small‐molecule by nucleic‐acid‐templated catalysis (NATC). The multiple components reversibility NATC, however, make it difficult apply vivo. Herein, we report use...
Supramolecular chemistry involves the non-covalent assembly of monomers into materials with unique properties and wide-ranging applications. Thermal analysis is a key analytical tool in this field, as it provides quantitative thermodynamic information on both structural stability nature underlying molecular interactions. However there exist many supramolecular systems whose kinetics are so slow under conditions approaching equilibrium that data inaccessible. We have developed simple rapid...
Supramolecular chemistry involves the non-covalent assembly of monomers into materials with unique properties and wide-ranging applications. Thermal analysis is a key analytical tool in this field, as it provides quantitative thermodynamic information on both structural stability nature underlying molecular interactions. However there exist many supramolecular systems whose kinetics are so slow under conditions approaching equilibrium that data inaccessible. We have developed simple rapid...
The chemical composition of extracellular polymeric substances (EPSs) secreted by Escherichia coli K12 in solution was monitored as a function time over various stages bacterial growth. We have observed that the spectra become enhanced at 1132 and 980 cm–1, which is attributed to an increasing fraction uronic nucleic acids within polymer matrix. Both these acidic molecules been shown sequester cations from neutralize their negative charge. discuss implication for this profile change terms...
Severe diseases such as the ongoing COVID-19 pandemic, well previous SARS and MERS outbreaks, are result of coronavirus infections have demonstrated urgent need for antiviral drugs to combat these deadly viruses. Due its essential role in viral replication function, 3CLpro has been identified a promising target development drugs. Previously reported SARS-CoV non-covalent inhibitors were used starting point covalent SARS-CoV-2 3CLpro. We report herein our efforts design synthesis which led...
Severe diseases such as the ongoing COVID-19 pandemic, well previous SARS and MERS outbreaks, are result of coronavirus infections have demonstrated urgent need for antiviral drugs to combat these deadly viruses. Due its essential role in viral replication function, 3CL<sup>pro</sup> has been identified a promising target development drugs. Previously reported SARS-CoV non-covalent inhibitors were used starting point covalent SARS-CoV-2 3CL<sup>pro</sup>. We report...