- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Probiotics and Fermented Foods
- Infant Nutrition and Health
- Chemical Synthesis and Analysis
- Bacteriophages and microbial interactions
- Microbial Metabolites in Food Biotechnology
- Proteoglycans and glycosaminoglycans research
- Digestive system and related health
- Monoclonal and Polyclonal Antibodies Research
- Gut microbiota and health
- Cancer Genomics and Diagnostics
- Antibiotic Resistance in Bacteria
- Enzyme Production and Characterization
- Colorectal Cancer Treatments and Studies
- Molecular Biology Techniques and Applications
- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- Breastfeeding Practices and Influences
- Lysosomal Storage Disorders Research
- Microfluidic and Capillary Electrophoresis Applications
- RNA modifications and cancer
- Nanopore and Nanochannel Transport Studies
- Advanced NMR Techniques and Applications
- Ion-surface interactions and analysis
University of Groningen
2013-2024
Leiden University
2009-2023
University Medical Center Groningen
2021
Massachusetts Institute of Technology
2014-2016
Netherlands Metabolomics Centre
2012
Avantium (Netherlands)
2009
A high-end label: Cyclophellitol aziridine-type activity-based probes allow for ultra-sensitive visualization of mammalian β-glucosidases (GBA1, GBA2, GBA3, and LPH) as well several non-mammalian (see picture). These offer new ways to study β-exoglucosidases, configurational isomers the cyclophellitol aziridine core may give targeting other retaining glycosidase families. Detailed facts importance specialist readers are published ”Supporting Information”. Such documents peer-reviewed, but...
The gastrointestinal tract (GIT) is colonized by a broad spectrum of microorganism, which bacteria are especially recognized for the health effects they exert. However insight in effector molecules on responsible still largely lacking. Recently, bacterial exopolysaccharides (EPS), glycan structures cell wall, have gained considerable attention their human health. EPS found to act as polymers that directly influence interactions with host, such adhesion GIT epithelium, immune responses, and...
Abstract Nanopores are single-molecule sensors used in nucleic acid analysis, whereas their applicability towards full protein identification has yet to be demonstrated. Here, we show that an engineered Fragaceatoxin C nanopore is capable of identifying individual proteins by measuring peptide spectra produced from hydrolyzed proteins. Using model proteins, the resulting experiments and mass spectrometry share similar profiles, hence allowing fingerprinting. The intensity peaks provides...
Although nanopores can be used for single-molecule sequencing of nucleic acids using low-cost portable devices, the characterization proteins and their modifications has yet to established. Here, we show that hydrophilic or glycosylated peptides translocate too quickly across FraC recognized. However, high ionic strengths (i.e., 3 M LiCl) low pH 3) together with a nanopore phenylalanine at its constriction allows recognition peptides, distinguish between mono- diglycosylated peptides. Using...
A big step towards routine: The title synthesis provides mannuronic acid alginate fragments featuring up to 12 cis-mannosidic linkages, in multi-milligram quantities (see scheme; Bn=benzyl, Lev=levulinoyl). Mannuronic building blocks were used a second-generation carbohydrate synthesizer secure the stereoselective introduction of β-mannosidic bonds fully automated fashion. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed,...
Well-defined fragments of hyaluronic acid (HA) have been obtained through a fully automated solid-phase oligosaccharide synthesis. Disaccharide building blocks, featuring disarmed glucuronic donor moiety and di-tert-butylsilylidene-protected glucosamine part, were used in the rapid efficient assembly HA up to pentadecamer level, equipped with conjugation-ready anomeric allyl function.
Scope Human milk oligosaccharides (hMOs) have beneficial effects on intestinal barrier function, but the mechanisms of action are not well understood. Here, hMOs goblet cells, which indicate that some may enhance mucus function through direct modulation cell studied. Methods and results The modulatory 2′‐fucosyllactose (2′‐FL), 3‐fucosyllactose (3‐FL), lacto‐ N ‐triaose II (LNT2), galacto‐oligosaccharides (GOS) expression secretory related genes MUC2 , TFF3 RETNLB Golgi‐sulfotransferase...
Insufficient intake of dietary fibers in Western societies is considered a major contributing factor the high incidence rates diabetes. The fiber pectin has been suggested to be beneficial for management both Diabetes Type 1 and 2, but mechanisms effects on insulin producing pancreatic β-cells are unknown. Our study aimed determine lemon pectins with different degree methyl-esterification (DM) under oxidative (streptozotocin) inflammatory (cytokine) stress elucidate underlying rescuing...
Activation of mannuronic acid esters leads to a conformational mixture alpha-anomeric triflates, in which the equatorial triflate ((1)C(4) chair) is formed preferentially. This unexpected intermediate clearly opposes anomeric effect and mainly stabilized by electron-withdrawing carboxylate function at C-5. Because center carries significant positive charge, (1)C(4) mannopyranosyl chair approximates favored (3)H(4) half-chair oxacarbenium ion conformation. The excellent beta-selectivity...
The O-acetylation of polysaccharides is a common modification used by pathogenic organisms to protect against external forces. Pseudomonas aeruginosa secretes the anionic, O-acetylated exopolysaccharide alginate during chronic infection in lungs cystic fibrosis patients form major constituent protective biofilm matrix. Four proteins have been implicated alginate, AlgIJF and AlgX. To probe biological function AlgJ, we determined its structure 1.83 Å resolution. AlgJ SGNH hydrolase-like...
Synthase-dependent secretion systems are a conserved mechanism for producing exopolysaccharides in Gram-negative bacteria. Although widely studied, it is not well understood how these organized to coordinate polymer biosynthesis, modification, and export across both membranes the peptidoglycan. To investigate synthase-dependent produce at molecular level, we determined crystal structure of AlgK-AlgX (AlgKX) complex involved Pseudomonas aeruginosa alginate exopolysaccharide acetylation...
Abstract The total synthesis of mixed‐sequence alginate oligosaccharides, featuring both β‐ D ‐mannuronic acid (M) and α‐ L ‐guluronic (G), is reported for the first time. A set GM, GMG, GMGM, GMGMG, GMGMGM, GMGMGMG, GMGGMG alginates was assembled using GM building blocks, having a guluronic acceptor part mannuronic donor side to allow fully stereoselective construction cis ‐glycosidic linkages. It found that nature reducing‐end anomeric center, which ten atoms away from reacting alcohol...
Human milk oligosaccharides (hMOs) are important bioactive components in mother contributing to infant health by supporting colonization and growth of gut microbes. Especially Bifidobacterium genus considered be supported hMOs. Approximately 200 different hMOs have been discovered characterized, but only a few abundant hMO can produced sufficient amounts applied formula. These usually supplied formula as single molecule it is unknown which how individual support bacteria. To investigate...
Hyaluronic acid (HA) is a naturally occurring polysaccharide that abundant in the extracellular matrix (ECM) of all vertebrate cells. HA-based hydrogels have attracted great interest for biomedical applications due to their high viscoelasticity and biocompatibility. In both ECM hydrogel applications, molecular weight (HMW)-HA can absorb large amount water yield matrices with level structural integrity. To understand underpinnings functional properties HA-containing hydrogels, few techniques...
Gut epithelial barrier disruption is commonly observed in Western diseases like diabetes and inflammatory bowel disease (IBD). Enhanced permeability triggers responses gut microbiota dysbiosis. Reduced bacterial diversity IBD affects metabolism, altering microbial products such as secondary bile acids (BAs), which potentially play a role regulation immunity. Dietary fibers pectin may substitute effects of these BAs. The study examines transepithelial electrical resistance T84 cells the gene...
The stereoselective synthesis of β-mannosides and the underlying reaction mechanism have been thoroughly studied, especially benzylidene-protected mannosides gained a lot attention since corresponding mannosyl triflates often give excellent selectivity. hypothesis for enhanced stereoselectivity has that benzylidene locks molecule in less reactive conformation with O6 trans to ring oxygen (O5), which would stabilize formed α-triflate subsequent β-selectivity. In this work, is challenged by...
The reactivity of a variety mannopyranosyl uronic acid donors was assessed in set competition experiments, which two (S)-tolyl mannosyl were made to compete for limited amount promoter (NIS/TfOH). These experiments revealed that the mannuronic is significantly higher than expected based on electron-withdrawing capacity C-5 carboxylic ester function. A 4-O-acetyl-β-(S)-tolyl donor found have similar as per-O-benzyl-α-(S)-tolyl mannose.
Abstract Phosphoglycosyltransferases (PGTs) are families of integral membrane proteins with intriguingly diverse architectures. These enzymes function to initiate many important biosynthetic pathways including those leading peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. In spite tremendous efforts, characterization these remains a challenge not only due the inherent difficulties associated purification but also limited availability convenient assays. Current PGT...