A5002850155- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Lysosomal Storage Disorders Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Analytical Chemistry and Chromatography
- Sphingolipid Metabolism and Signaling
- Cocoa and Sweet Potato Agronomy
- Cellular transport and secretion
- Enzyme Production and Characterization
- Food Chemistry and Fat Analysis
- Biochemical Analysis and Sensing Techniques
- Biosimilars and Bioanalytical Methods
- Antifungal resistance and susceptibility
- Protein purification and stability
- Cystic Fibrosis Research Advances
- Proteins in Food Systems
- Proteoglycans and glycosaminoglycans research
- Pesticide Residue Analysis and Safety
- Diet, Metabolism, and Disease
- Electron Spin Resonance Studies
- thermodynamics and calorimetric analyses
- Flood Risk Assessment and Management
- Autoimmune and Inflammatory Disorders Research
- Retinoids in leukemia and cellular processes
Mondelēz International (United Kingdom)
2017-2021
Reading Museum
2021
Quotient Clinical (United Kingdom)
2012-2014
University of Oxford
1991-2012
Fordham University
2012
Fox Chase Cancer Center
2003
University of California, San Francisco
1996-1998
University of Dundee
1994-1996
Oxford Research Group
1991
We show that hepatitis C virus (HCV) p7 protein forms ion channels in black lipid membranes. HCV are inhibited by long-alkyl-chain iminosugar derivatives, which have antiviral activity against the surrogate bovine viral diarrhea virus. presents a potential target for therapy.
Abstract The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes an apical membrane C1 − channel regulated by protein phosphorylation. To identify cAMP‐dependent kinase (PKA)‐phosphorylated residues in full‐length CFTR, immobilized metal‐ion affinity chromatography (IMAC) was used to selectively purify phosphopeptides. greater specificity of iron‐loaded (Fe 3+ ) nitrilotriacetic (NTA) Sepharose compared iminodiacetic acid (IDA) metal‐chelating matrices demonstrated using...
Glycosphingolipids are endocytosed and targeted to the Golgi apparatus but mistargeted lysosomes in sphingolipid storage disorders. Substrate reduction therapy utilizes imino sugars inhibit glucosylceramide synthase potentially abrogate effects of storage. Niemann-Pick type C (NPC) disease is a disorder intracellular transport where glycosphingolipids (GSLs) cholesterol accumulate endosomal compartments. The mechanisms altered trafficking not known may involve mistargeting disrupted function...
Development of invariant natural killer T (iNKT) cells requires the presentation lipid ligand(s) by CD1d molecules in thymus. The glycosphingolipid (GSL) isoglobotrihexosylceramide (iGb3) has been proposed as iNKT cell-selecting ligand thymus and to be involved peripheral activation dendritic (DCs). However, there is no direct biochemical evidence for presence iGb3 mouse or human DCs. Using a highly sensitive HPLC assay, only tissue where could detected was dorsal root ganglion (DRG). not...
Elimination of the binding immunoglobulin Fc to gamma receptors (FcγR) is highly desirable for avoidance unwanted inflammatory responses therapeutic antibodies and fusion proteins. Many different approaches have been described in literature but none them completely eliminates all Fcγ receptors. Here we describe a set novel variants having specific amino acid substitutions region at L234 L235 combined with substitution G236R. They show no detectable or C1q, are inactive functional cell-based...
Abstract The GM2 gangliosidoses are caused by incomplete catabolism of ganglioside in the lysosome, leading to progressive storage and a neurodegenerative clinical course. An inflammatory response (microglial activation, macrophage infiltration, oxidative damage) has been found be consequence brain, although it remains unclear whether this contributes pathogenesis or disease progression. In study, we treated Sandhoff mice with nonsteroidal antiinflammatory drugs (indomethacin, aspirin,...
Abstract Exceptional rainfall during the summer of 2007 caused widespread flooding in parts England. While focus attention has been correctly placed on impact densely populated urban areas, large tracts rural land were seriously affected by flooding. Summer is particularly damaging to farming. This paper presents results from an evaluation impacts flood events agriculture. High financial losses incurred horticultural sector. Arable farmers direct form crop loss or yield reduction due and...
The inhibition of ER (endoplasmic reticulum) alpha-glucosidases I and II by imino sugars, including NB-DNJ (N-butyl-deoxynojirimycin), causes the retention glucose residues on N-linked oligosaccharides. Therefore, normal glycoprotein trafficking processing through glycosylation pathway is abrogated glycoproteins are directed to undergo ERAD (ER-associated degradation), a consequence which production cytosolic FOS (free oligosaccharides). Following treatment with NB-DNJ, were extracted from...
Myeloid antigen-presenting cells (APC) express CD1d molecules that present exogenous and endogenous lipid antigens activate CD1d-restricted T cells, natural killer (NKT) cells. NKT cell activation has been shown to mediate the potent downstream of other immune through cell–cell interactions rapid, prolific cytokine production. Foreign are not required for activation. The lipids bound sufficient in setting Toll-like receptor-induced cytokines. most identified glycosphingolipids (GSL). GSL...
Fluorescent labeling of oligosaccharides with anthranilic acid (2-aminobenzoic acid; 2AA), or 2-aminobenzamide (2AB) permits the rapid, sensitive analysis structures present in cells and tissues. Normal-phase (NP)/hydrophilic interaction chromatography (HILIC) is commonly used to separate fluorophore-derivatized oligosaccharides. Column elution expressed as glucose units (GU) following calculation relative retention when compared an external oligomer standard. However, there significant...
The major diagnostic antigen of Paracoccidioides brasiliensis is the exocellularly secreted 43,000 Da glycoprotein (gp43) which contains a single N-linked oligosaccharide chain. This oligosaccharide, although poorly immunogenic in man, responsible for cross-reactivity gp43 with sera from patients histoplasmosis, and may have role fungal virulence. It neutral high-mannose core (Man7GlcNAc2) to (1-->6)-linked alpha-D-Manp chain variable length, substituted at 2-O positions by residues,...
An alpha-fucosidase has been extracted from almond meal and purified 163,000-fold to apparent homogeneity using a novel affinity ligand, N-(5-carboxy-1-pentyl)-1,5-dideoxy-1,5-imino-L-fucitol, coupled Affi-Gel 102. Substrate specificity studies demonstrate that the enzyme hydrolyzes alpha-fucosidic linkages in Gal(beta 1----3)(Fuc(alpha 1----4]GlcNAc(beta 1----3)Gal(beta 1----4)Glc 1----4)(Fuc(alpha 1----3]GlcNAc(beta at similar rates but is unable hydrolyze Fuc(alpha 1----2)Gal,...
Background: Several new products have been marketed with the specific capability of removing phospholipids. These were evaluated alongside more traditional extraction techniques, using UHPLC and precursor-ion scanning (pre m/z 184), which detects glycerophosphocholines (GPCho), lyso-GPCho sphingomyelins. Using this technique plasma GPCho profile human, dog rat is briefly compared. Results: Precursor-ion detected phospholipid in extracts than a SRM experiment (m/z 184–184). Products designed...
In the accompanying paper [Mellor, Neville, Harvey, Platt, Dwek and Butters (2004) Biochem. J. 381, 861–866] we treated HL60 cells with N-alk(en)yl-deoxynojirimycin (DNJ) compounds to inhibit glucosphingolipid (GSL) biosynthesis identified a number of non-GSL-derived, small, free oligosaccharides (FOS) most likely produced due inhibition oligosaccharide-processing enzymes α-glucosidases I II. When were concentrations N-alk(en)ylated DNJ analogues that inhibited GSL completely, N-butyl-...
Deoxynojirimycin (DNJ) analogues are inhibitors of ceramide glucosyltransferase (CGT), which catalyses the first step in glucosphingolipid (GSL) biosynthetic pathway. We have synthesized a series DNJ to study contribution N-alk(en)yl side chains (C4, C9 or C18) behaviour these cultured HL60 cells. When cells were treated for 16 h at non-cytotoxic concentrations inhibitor, 40–50% decrease GSL levels was measured by HPLC analysis GSL-derived oligosaccharides following glycanase digestion and...
To study interactions between the contiguous NBD1 and R domains of CFTR, wild-type DeltaF508 NBD1-R (amino acids 404-830, in fusion with His6 tag) were expressed as single proteins Escherichia coli. (10-25 mg/L culture) was purified from inclusion bodies 8 M urea by Ni-affinity chromatography, renatured rapid dilution at pH 5. In vitro phosphorylation protein kinase A increased apparent size approximately 52 to 56 kDa SDS-PAGE. The fluorescent ATP analogue TNP-ATP bound 0.81 +/- 0.1 microM...
Invariant NKT (iNKT) cells are a subset of highly conserved immunoregulatory T that modify variety immune responses, including alloreactivity. Central to their function is the interaction invariant TCR with glycosphingolipid (GSL) ligands presented by nonpolymorphic MHC class I molecule CD1d and ability secrete rapidly large amounts immunomodulatory cytokines when activated. Whether iNKT cells, like NK conventional can directly display alloreactivity not known. We show in this study human...
Abstract Cocoa seed storage proteins play an important role in flavour development as aroma precursors are formed from their degradation during fermentation. Major the beans of Theobroma cacao belonging to vicilin and albumin classes. Although both these classes have been extensively characterized, there is still limited information on expression abundance other present cocoa beans. This work first attempt characterize whole bean proteome by nano‐UHPLC‐ESI MS/MS analysis using tryptic...