A5000015700- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- vaccines and immunoinformatics approaches
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Pharmacogenetics and Drug Metabolism
- Biochemical Analysis and Sensing Techniques
- Pharmacological Receptor Mechanisms and Effects
- Viral Infections and Outbreaks Research
- Atmospheric chemistry and aerosols
- Protease and Inhibitor Mechanisms
- Inflammasome and immune disorders
- Molecular Sensors and Ion Detection
- Organic Chemistry Cycloaddition Reactions
- Monoclonal and Polyclonal Antibodies Research
- Odor and Emission Control Technologies
- Gout, Hyperuricemia, Uric Acid
- Tryptophan and brain disorders
- Click Chemistry and Applications
- Asymmetric Synthesis and Catalysis
- Supramolecular Chemistry and Complexes
University of Oxford
2019-2023
Australian Regenerative Medicine Institute
2023
Monash University
2023
Alzheimer’s Research UK
2019-2020
Discovery Institute
2020
Target (United States)
2020
Science Oxford
2020
McGill University
2012-2019
Université Libre de Bruxelles
2012
Abstract Although drug development typically focuses on binding thermodynamics, recent studies suggest that kinetic properties can strongly impact a candidate’s efficacy. Robust techniques for measuring inhibitor association and dissociation rates are therefore essential. To address this need, we have developed pair of complementary isothermal titration calorimetry (ITC) the kinetics enzyme inhibition. The advantages ITC over standard include speed, generality, versatility; also measures...
The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight importance of increasing preparedness for viral disease outbreaks providing rapid prevention treatment strategies. NSP3 macrodomain coronaviruses including SARS-CoV-2 is among protein repertoire that was identified as a potential target development antiviral agents, due to its critical role in replication consequent pathogenicity host. By combining virtual biophysical screening efforts, we...
Our docking program, Fitted, implemented in our computational platform, Forecaster, has been modified to carry out automated virtual screening of covalent inhibitors. With this version the and further docking-based optimization a selected hit led identification potential reversible inhibitors prolyl oligopeptidase activity. After visual inspection, molecule together with four analogues were for synthesis made one-five chemical steps. Biological evaluations on recombinant POP FAPα enzymes,...
Bicyclic chiral scaffolds are privileged motifs in medicinal chemistry. Over the years, we have reported covalent bicyclic prolyl oligopeptidase inhibitors that were highly selective for POP over a number of homologous proteins. Herein, wish to report structure-based design and synthesis novel class based on hexahydroisoindoles. A docking study guided selection structures synthesis. The stereochemistry, decoration, position within molecule assessed virtually. Following best candidates, vitro...
When trying to identify new potential therapeutic protein targets, access data and knowledge is increasingly important. In a field where resources sources become available every day, it crucial be able take step back look at the wider picture in order drug targets. While this task routinely performed by bespoke literature searches, often time-consuming lacks uniformity when comparing multiple targets one time. To address challenge, we developed TargetDB, tool that aggregates public...
The NLRP3 inflammasome regulates production of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, contributes to inflammation exacerbating disease.
The ipso-nitration of calix[6]arene-based molecular receptors is a important synthetic pathway for the elaboration more sophisticated systems. This reaction has been studied variety capped calixarenes, and general trend regioselective nitration three aromatic units out six in moderate to high yield observed. selectivity is, part, attributed electronic connection between protonated cap at small rim reactive sites large rim. In addition, this work highlights fact that subtle conformational...
Over the past decade, there has been increasing interest in covalent inhibition as a drug design strategy. Our own development of prolyl oligopeptidase (POP) and fibroblast activation protein α (FAP) inhibitors led us to question whether these two serine proteases were equal terms their reactivity toward electrophilic warheads. To streamline such investigations, we exploited both computational experimental methods investigate influence different reactive groups on potency binding kinetics...
ABSTRACT When trying to identify new potential therapeutic targets, access data and knowledge is increasingly important. In a field where resources sources become available every day, it crucial be able take step back look at the wider picture in order drug targets. While this task routinely performed by bespoke researchers, often time-consuming lacks uniformity when one wants compare multiple targets same time. Therefore we developed TargetDB, tool that aggregates public information on...
Abstract The melanocortin receptor 4 (MC4R) belongs to the family of G-protein coupled receptors and is a key switch in leptin-melanocortin molecular axis that controls hunger satiety. Brain-produced hormones such as α-melanocyte-stimulating hormone (agonist) agouti-related peptide (inverse agonist) regulate communication MC4R but are promiscuous for subtypes induce wide array biological effects. Using conformation-selective ConfoBody, use active state-stabilized facilitated efficient de...