A5087994751- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Catalytic Cross-Coupling Reactions
- Tryptophan and brain disorders
- Cholinesterase and Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Marine Toxins and Detection Methods
- Lipid Membrane Structure and Behavior
- Virus-based gene therapy research
- 14-3-3 protein interactions
- Evolutionary Psychology and Human Behavior
- Microbial metabolism and enzyme function
- Bacteriophages and microbial interactions
- Innovative Microfluidic and Catalytic Techniques Innovation
- Click Chemistry and Applications
- Gene Regulatory Network Analysis
- Bacterial biofilms and quorum sensing
- RNA Interference and Gene Delivery
- Bacterial Genetics and Biotechnology
- Cancer-related Molecular Pathways
- Respiratory viral infections research
- Protein purification and stability
University of Cambridge
2011-2022
École Polytechnique Fédérale de Lausanne
2020
MRC Cancer Unit
2016-2017
Sulfonated cyclodextrins show nontoxic, broad-spectrum virucidal activity in vitro, ex vivo, and vivo.
Abstract The essential mitotic kinase Aurora A (AURKA) is controlled during cell cycle progression via two distinct mechanisms. Following activation loop autophosphorylation early in mitosis when it localizes to centrosomes, AURKA allosterically activated on the spindle binding microtubule-associated protein, TPX2. Here, we report discovery of AurkinA, a novel chemical inhibitor AURKA-TPX2 interaction, which acts an unexpected structural mechanism inhibit activity and localization. In...
Abstract Small‐molecule modulators of biological targets play a crucial role in biology and medicine. In this context, diversity‐oriented synthesis (DOS) provides strategies toward generating small molecules with broad range unique scaffolds, hence three‐dimensionality, to target area space. study, an organocatalysis‐derived DOS library macrocycles was synthesized by exploiting the pluripotency aldehydes. The orthogonal combination multiple diversity‐generating organocatalytic steps alkene...
Pseudomonas aeruginosa is an opportunistic pathogen capable of group behaviors, including biofilm formation and swarming motility. These behaviors are regulated by both the intracellular signaling molecule c-di-GMP acylhomoserine lactone quorum-sensing systems. Here, we show that quinolone signal (PQS) system also contributes to regulation Specifically, our data indicate 2-heptyl-4-quinolone (HHQ), a precursor PQS, likely induces production phenazine-1-carboxylic acid (PCA), which in turn...
Stapled peptides have great potential as modulators of protein–protein interactions (PPIs). However, there is a vast landscape chemical features that can be varied for any given peptide, and identifying set maximizes cellular uptake subsequent target engagement remains key challenge. Herein, we present systematic analysis staple functionality on the peptide bioactivity in assays. Through application "toolbox" diversified dialkynyl linkers to stapling MDM2-binding via double-click approach,...
Abstract Small‐molecule modulators of biological targets play a crucial role in biology and medicine. In this context, diversity‐oriented synthesis (DOS) provides strategies toward generating small molecules with broad range unique scaffolds, hence three‐dimensionality, to target area space. study, an organocatalysis‐derived DOS library macrocycles was synthesized by exploiting the pluripotency aldehydes. The orthogonal combination multiple diversity‐generating organocatalytic steps alkene...
Computational binding free energy predictions were validated against experiment and used to design new inhibitors of an important protein–protein interaction.
Abstract Inhibiting the aggregation of amyloid β (1-42) is a promising strategy for development disease-modifying Alzheimer’s disease therapeutics. To date, however, no sufficiently efficacious inhibitors have been identified, despite best efforts >200 advanced drug campaigns. This failure can be attributed to limitations in current compound screening and vivo validation assays. Here, we report an vitro platform based on use fluorescence lifetime sensor. The microfluidic “nanoFLIM” assay...
Abstract Inhibiting the aggregation of amyloid β (1-42) is a promising strategy for development disease-modifying Alzheimer’s disease therapeutics. To date, however, no sufficiently efficacious inhibitors have been identified, despite best efforts >200 advanced drug campaigns. This failure can be attributed to limitations in current compound screening and vivo validation assays. Here, we report an vitro platform based on use fluorescence lifetime sensor. The microfluidic “nanoFLIM” assay...
Abstract Key features of the strategy are NHC‐mediated organocoupling and Grubbs‐catalyzed metathesis reaction.