A5072460427- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Enzyme Production and Characterization
- Bacterial biofilms and quorum sensing
- Pancreatic function and diabetes
- Genomics and Phylogenetic Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Cannabis and Cannabinoid Research
- SARS-CoV-2 and COVID-19 Research
- Enzyme Catalysis and Immobilization
- Peroxisome Proliferator-Activated Receptors
- Calcium signaling and nucleotide metabolism
- Natural Antidiabetic Agents Studies
- Endoplasmic Reticulum Stress and Disease
- Synthesis and Catalytic Reactions
Leiden University
2020-2025
Oncode Institute
2020
During infection, the human opportunistic pathogen Pseudomonas aeruginosa forms protective biofilms, whose matrix consists of proteins, nucleic acids, and polysaccharides such as alginate, Psl, Pel. a polymeric pentasaccharide composed mannose, rhamnose, glucose, is produced during early stages biofilm formation, serving barrier against antibiotics immune system. The Psl biosynthesis gene cluster, besides encoding various glycosyltransferases, also includes an endoglycosidase, PslG. Here, we...
Abstract The assembly of complex bacterial glycans presenting rare structural motifs and cis ‐glycosidic linkages is significantly obstructed by the lack knowledge reactivity constituting building blocks stereoselectivity reactions in which they partake. We here report a strategy to map carbohydrate apply it understand sugar, caryophyllose, C12‐monosaccharide, containing characteristic tetrasubstituted stereocenter. mapped reactivity–stereoselectivity relationships for caryophyllose donor...
The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists five members, which are involved in the Ca2+-independent production N-acylphosphatidylethanolamines (NAPEs). NAPEs lipid precursors for bioactive N-acylethanolamines (NAEs) that various physiological processes such as food intake, pain, inflammation, stress, anxiety. Recently, we identified α-ketoamides first pan-active PLAAT inhibitor scaffold reduced arachidonic acid levels PLAAT3-overexpressing U2OS...
Glycoside hydrolases (glycosidases) take part in myriad biological processes and are important therapeutic targets. Competitive mechanism-based inhibitors useful tools to dissect their role comprise a good starting point for drug discovery. The natural product, cyclophellitol, mechanism-based, covalent irreversible retaining β-glucosidase inhibitor has inspired the design of diverse α- β-glycosidase activity-based probe scaffolds. Here, we sought deepen our understanding structural...
The combined inhibition of endoplasmic reticulum (ER) α-glucosidases I and II has been shown to inhibit replication a broad range viruses that rely on ER protein quality control. We found, by screening panel deoxynojirimycin cyclitol glycomimetics, the mechanism-based α-glucosidase inhibitor, 1,6-epi-cyclophellitol cyclosulfate, potently blocks SARS-CoV-2 in lung epithelial cells, halting intracellular generation mature spike protein, reducing production infectious progeny, leading reduced...
Abstract The assembly of complex bacterial glycans presenting rare structural motifs and cis ‐glycosidic linkages is significantly obstructed by the lack knowledge reactivity constituting building blocks stereoselectivity reactions in which they partake. We here report a strategy to map carbohydrate apply it understand sugar, caryophyllose, C12‐monosaccharide, containing characteristic tetrasubstituted stereocenter. mapped reactivity–stereoselectivity relationships for caryophyllose donor...
Cyclophellitols are potent inhibitors of exo- and endoglycosidases. Efficient synthetic methodologies needed to fully capitalize on this intriguing class mechanism-based enzyme deactivators. We report the synthesis an orthogonally protected cyclitol from d-glucal (19% yield over 12 steps) its use in α-(1,3)-linked di- trisaccharide dextran mimetics. These new glycomimetics may find as Dextranase inhibitors, developed chemistries widening palette glycoprocessing enzyme-targeting glycomimetics.
Abstract Cyclophellitol aziridines have found wide application as mechanism‐based, covalent, and irreversible inhibitors of retaining glycosidases. These compounds, like their parent compound, cyclophellitol (a natural product β‐glucosidase inactivator), make use the mechanism action glycosidases, which process substrate through formation a transient covalent intermediate. In contrast, inverting other main family glycosyl hydrolases, do not employ such intermediate, and, consequence, useful...