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Urological Research 1985The adherence of piliated strains of Escherichia coli (E. coli) to mammalian epithelial cells has been reported by several investigators to be specifically inhibited by... (Comparative Study)
Comparative Study
The adherence of piliated strains of Escherichia coli (E. coli) to mammalian epithelial cells has been reported by several investigators to be specifically inhibited by D(+)-mannose or its derivatives. Much of this work utilized mannose type compounds to inhibit agglutination of mannan containing yeast cells by E. coli to demonstrate mannose sensitivity. This report investigates the ability of the neotype strain of E. coli (which is sensitive to mannose inhibition of yeast cell agglutination) to bind and metabolize radiolabeled D(+)-mannose. In addition the relative efficacy of D(+)-mannose and heparin to inhibit the adherence of E. coli to rabbit bladder mucosa was compared. Results showed that although D(+)-mannose did block E. coli--yeast cell agglutination in a reversible manner, radiolabeled D(+)-mannose binding by E. coli could not be displaced by 1,000 fold excess unlabeled D(+)-mannose. This suggests uptake of the sugar as opposed to a surface binding phenomenon which was confirmed by the demonstration of significant metabolism of mannose by E. coli. The same concentration of D(+)-mannose which prevented E. coli--yeast cell agglutination was not particularly effective in preventing E. coli adherence to the acid denuded rabbit bladder. Heparin treatment of the acid denuded bladder was very effective in preventing E. coli adherence but was ineffective in preventing E. coli--yeast cell agglutination. This indicates that E. coli--yeast cell agglutination should not be correlated with E. coli adherence to mammalian epithelial tissue.
Topics: Agglutination; Animals; Binding Sites; Candida albicans; Epithelium; Escherichia coli; Heparin; Male; Mannose; Rabbits; Urinary Bladder
PubMed: 3892841
DOI: 10.1007/BF00261571 -
Biochimica Et Biophysica Acta Oct 2001Dietary mannose is used to treat glycosylation deficient patients with mutations in phosphomannose isomerase (PMI), but there is little information on mannose metabolism...
Dietary mannose is used to treat glycosylation deficient patients with mutations in phosphomannose isomerase (PMI), but there is little information on mannose metabolism in model systems. We chose the mouse as a vertebrate model. Intravenous injection of [2-3H]mannose shows rapid equilibration with the extravascular pool and clearance t(1/2) of 28 min with 95% of the label catabolized via glycolysis in <2 h. Labeled glycoproteins appear in the plasma after 30 min and increase over 3 h. Various organs incorporate [2-3H]mannose into glycoproteins with similar kinetics, indicating direct transport and utilization. Liver and intestine incorporate most of the label (75%), and the majority of the liver-derived proteins eventually appear in plasma. [2-3H]Mannose-labeled liver and intestine organ cultures secrete the majority of their labeled proteins. We also studied the long-term effects of mannose supplementation in the drinking water. It did not cause bloating, diarrhea, abnormal behavior, weight gain or loss, or increase in hemoglobin glycation. Organ weights, histology, litter size, and growth of pups were normal. Water intake of mice given 20% mannose in their water was reduced to half compared to other groups. Mannose in blood increased up to 9-fold (from 100 to 900 microM) and mannose in milk up to 7-fold (from 75 to 500 microM). [2-3H]Mannose clearance, organ distribution, and uptake kinetics and hexose content of glycoproteins in organs were similar in mannose-supplemented and non-supplemented mice. Mannose supplements had little effect on the specific activity of phosphomannomutase (Man-6-P<-->Man-1-P) in different organs, but specific activity of PMI in brain, intestine, muscle, heart and lung gradually increased <2-fold with increasing mannose intake. Thus, long-term mannose supplementation does not appear to have adverse effects on mannose metabolism and mice safely tolerate increased mannose with no apparent ill effects.
Topics: Administration, Oral; Animals; Animals, Newborn; Body Weight; Dietary Supplements; Dose-Response Relationship, Drug; Female; Glycoproteins; Injections, Intravenous; Mannose; Mannose-6-Phosphate Isomerase; Mice; Milk; Models, Animal; Organ Culture Techniques; Phosphotransferases (Phosphomutases); Pregnancy; Time Factors; Tritium
PubMed: 11687298
DOI: 10.1016/s0304-4165(01)00183-0 -
Assay and Drug Development Technologies 2020The main challenging aspect in the management of tuberculosis (TB) diseases is effective alveolar macrophages targeting. Macrophage mannose receptor plays a predominant...
The main challenging aspect in the management of tuberculosis (TB) diseases is effective alveolar macrophages targeting. Macrophage mannose receptor plays a predominant role in stimulating immune systems by TB pathogen. Our earlier computational studies revealed that O-stearoyl mannose (OSM) possesses a higher affinity with macrophage mannose receptors. Therefore, keeping this in view, we developed OSM with the association of stearic acid and d-mannose as initial reactants by the esterification process. Preliminary confirmation of reaction was assessed with thin-layer chromatography experimentation, whereas further confirmation followed by characterization with several analytical experimental tools such as fourier transform near-infrared, differential scanning calorimetry, and electrospray ionization-assisted mass spectrometry confirms the formation of the OSM. This synthesized and well-characterized OSM as a ligand was further incubated with surface-engineered lipid nanoarchitectonics to achieve OSM ligand-engineered lipid nanoarchitectonics and earlier explored for its safety study through hemolysis assay and potential triggering efficiency in human alveolar macrophages (THP-1 cells) to validate its active targeting efficiency. Graphical Abstract [Figure: see text].
Topics: Humans; Ligands; Lipids; Macrophages, Alveolar; Mannose; Molecular Structure; Nanostructures; Nanotechnology; Stearic Acids; Tuberculosis
PubMed: 32941071
DOI: 10.1089/adt.2020.999 -
Molecular & Cellular Proteomics : MCP Jan 2011Alteration in glycosylation has been observed in cancer. However, monitoring glycosylation changes during breast cancer progression is difficult in humans. In this...
Alteration in glycosylation has been observed in cancer. However, monitoring glycosylation changes during breast cancer progression is difficult in humans. In this study, we used a well-characterized transplantable breast tumor mouse model, the mouse mammary tumor virus-polyoma middle T antigen, to observe early changes in glycosylation. We have previously used the said mouse model to look at O-linked glycosylation changes with breast cancer. In this glycan biomarker discovery study, we examined N-linked glycan variations during breast cancer progression of the mouse model but this time doubling the number of mice and blood draw points. N-glycans from total mouse serum glycoproteins were profiled using matrix-assisted laser desorption/ionization Fourier transform-ion cyclotron resonance mass spectrometry at the onset, progression, and removal of mammary tumors. We observed four N-linked glycans, m/z 1339.480 (Hex(3)HexNAc), 1485.530 (Hex(3)HexNAc(4)Fuc), 1809.639 (Hex(5)HexNAc(4)Fuc), and 1905.630 (Man(9)), change in intensity in the cancer group but not in the control group. In a separate study, N-glycans from total human serum glycoproteins of breast cancer patients and controls were also profiled. Analysis of human sera using an internal standard showed the alteration of the low-abundant high-mannose glycans, m/z 1419.475, 1581.528, 1743.581, 1905.634 (Man(6-9)), in breast cancer patients. A key observation was the elevation of a high-mannose type glycan containing nine mannoses, Man(9), m/z 1905.630 in both mouse and human sera in the presence of breast cancer, suggesting an incompletion of the glycosylation process that normally trims back Man(9) to produce complex and hybrid type oligosaccharides.
Topics: Animals; Breast Neoplasms; Carbohydrate Conformation; Disease Progression; Female; Humans; Mannose; Mice; Neoplasm Metastasis; Polysaccharides; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 21097542
DOI: 10.1074/mcp.M110.002717 -
Mannose 6-sulfate is present in the N-linked oligosaccharides of lysosomal enzymes of Dictyostelium.Archives of Biochemistry and Biophysics Dec 1985The major N-linked, anionic oligosaccharide found on several lysosomal enzymes of Dictyostelium discoideum contains five charges, composed of three sulfate esters and...
The major N-linked, anionic oligosaccharide found on several lysosomal enzymes of Dictyostelium discoideum contains five charges, composed of three sulfate esters and two residues of Man-6-P in phosphodiester linkage. Most of the SO4 was found as Man-6-SO4. This novel sulfated sugar was detected and quantitated by measuring the appearance of 3,6-anhydromannitol following acid hydrolysis and reduction of base-treated, reduced oligosaccharides. If SO4 is removed by solvolysis prior to the base treatment, the anhydrosugar is not formed, indicating that its presence is not an artifact of the procedure. That these oligosaccharides are derived from standard high-mannose-type oligosaccharides indicates that only one or, at most, two Man residues are unsubstituted at the 6-position.
Topics: Binding Sites; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Dictyostelium; Hexosaminidases; Lysosomes; Mannose; Mannosidases; Oligosaccharides; alpha-Mannosidase; beta-Glucosidase; beta-N-Acetylhexosaminidases
PubMed: 2935083
DOI: 10.1016/0003-9861(85)90547-8 -
Molecules (Basel, Switzerland) May 2022l-Hexoses are important components of biologically relevant compounds and precursors of some therapeuticals. However, they typically cannot be obtained from natural...
l-Hexoses are important components of biologically relevant compounds and precursors of some therapeuticals. However, they typically cannot be obtained from natural sources and due to the complexity of their synthesis, their commercially available derivatives are also very expensive. Starting from one of the cheapest d-hexoses, d-mannose, using inexpensive and readily available chemicals, we developed a reaction pathway to obtain two orthogonally protected l-hexose thioglycoside derivatives, l-gulose and l-galactose, through the corresponding 5,6-unsaturated thioglycosides by C-5 epimerization. From these derivatives, the orthogonally protected thioglycosides of further two l-hexoses (l-allose and l-glucose) were synthesized by C-4 epimerization. The preparation of the key intermediates, the 5,6-unsaturated derivatives, was systematically studied using various protecting groups. By the method developed, we are able to produce highly functionalized l-gulose derivatives in 9 steps (total yields: 21-23%) and l-galactose derivatives in 12 steps (total yields: 6-8%) starting from d-mannose.
Topics: Galactose; Hexoses; Mannose; Thioglycosides
PubMed: 35684360
DOI: 10.3390/molecules27113422 -
Molecular Aspects of Medicine Oct 2016Proteins are frequently modified by complex carbohydrates (glycans) that play central roles in maintaining the structural and functional integrity of cells and tissues... (Review)
Review
Proteins are frequently modified by complex carbohydrates (glycans) that play central roles in maintaining the structural and functional integrity of cells and tissues in humans and lower organisms. Mannose forms an essential building block of protein glycosylation, and its functional involvement as components of larger and diverse α-mannosidic glycoepitopes in important intra- and intercellular glycoimmunological processes is gaining recognition. With a focus on the mannose-rich asparagine (N-linked) glycosylation type, this review summarises the increasing volume of literature covering human and non-human protein mannosylation, including their structures, biosynthesis and spatiotemporal expression. The review also covers their known interactions with specialised host and microbial mannose-recognising C-type lectin receptors (mrCLRs) and antibodies (mrAbs) during inflammation and pathogen infection. Advances in molecular mapping technologies have recently revealed novel immuno-centric mannose-terminating truncated N-glycans, termed paucimannosylation, on human proteins. The cellular presentation of α-mannosidic glycoepitopes on N-glycoproteins appears tightly regulated; α-mannose determinants are relative rare glycoepitopes in physiological extracellular environments, but may be actively secreted or leaked from cells to transmit potent signals when required. Simultaneously, our understanding of the molecular basis on the recognition of mannosidic epitopes by mrCLRs including DC-SIGN, mannose receptor, mannose binding lectin and mrAb is rapidly advancing, together with the functional implications of these interactions in facilitating an effective immune response during physiological and pathophysiological conditions. Ultimately, deciphering these complex mannose-based receptor-ligand interactions at the detailed molecular level will significantly advance our understanding of immunological disorders and infectious diseases, promoting the development of future therapeutics to improve patient clinical outcomes.
Topics: Animals; Bacterial Infections; Carbohydrate Sequence; Glycoproteins; Glycosylation; Humans; Immune System Diseases; Inflammation; Lectins, C-Type; Mannose; Models, Immunological; Models, Molecular; Mycoses; Neoplasms
PubMed: 27086127
DOI: 10.1016/j.mam.2016.04.004 -
Acta Crystallographica. Section D,... Jul 2023Mannose 2-epimerase (ME), a member of the acylglucosamine 2-epimerase (AGE) superfamily that catalyzes epimerization of D-mannose and D-glucose, has recently been...
Mannose 2-epimerase (ME), a member of the acylglucosamine 2-epimerase (AGE) superfamily that catalyzes epimerization of D-mannose and D-glucose, has recently been characterized to have potential for D-mannose production. However, the substrate-recognition and catalytic mechanism of ME remains unknown. In this study, structures of Runella slithyformis ME (RsME) and its D254A mutant [RsME(D254A)] were determined in their apo forms and as intermediate-analog complexes [RsME-D-glucitol and RsME(D254A)-D-glucitol]. RsME possesses the (α/α)-barrel of the AGE superfamily members but has a unique pocket-covering long loop (loop). The RsME-D-glucitol structure showed that loop moves towards D-glucitol and closes the active pocket. Trp251 and Asp254 in loop are only conserved in MEs and interact with D-glucitol. Kinetic analyses of the mutants confirmed the importance of these residues for RsME activity. Moreover, the structures of RsME(D254A) and RsME(D254A)-D-glucitol revealed that Asp254 is vital for binding the ligand in a correct conformation and for active-pocket closure. Docking calculations and structural comparison with other 2-epimerases show that the longer loop in RsME causes steric hindrance upon binding to disaccharides. A detailed substrate-recognition and catalytic mechanism for monosaccharide-specific epimerization in RsME has been proposed.
Topics: Mannose; Racemases and Epimerases; Substrate Specificity; Carbohydrate Epimerases
PubMed: 37314406
DOI: 10.1107/S205979832300390X -
Analytica Chimica Acta May 2020Many industrial enzymes exhibit macro- and micro-heterogeneity due to co-occurring post-translational modifications. The resulting proteoforms may have different...
Many industrial enzymes exhibit macro- and micro-heterogeneity due to co-occurring post-translational modifications. The resulting proteoforms may have different activity and stability and, therefore, the characterization of their distributions is of interest in the development and monitoring of enzyme products. Protein glycosylation may play a critical role as it can influence the expression, physical and biochemical properties of an enzyme. We report the use of hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) to profile intact glycoform distributions of high mannose-type N-glycosylated proteins, using an industrially produced fungal lipase for the food industry as an example. We compared these results with conventional reversed phase LC-MS (RPLC-MS) and sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE). HILIC appeared superior in resolving lipase heterogeneity, facilitating mass assignment of N-glycoforms and sequence variants. In order to understand the glycoform selectivity provided by HILIC, fractions from the four main HILIC elution bands for lipase were taken and subjected to SDS-PAGE and bottom-up proteomic analysis. These analyses enabled the identification of the most abundant glycosylation sites present in each fraction and corroborated the capacity of HILIC to separate protein glycoforms based on the number of glycosylation sites occupied. Compared to RPLC-MS, HILIC-MS reducted the sample complexity delivered to the mass spectrometer, facilitating the assignment of the masses of glycoforms and sequence variants as well as increasing the number of glycoforms detected (69 more proteoforms, 177% increase). The HILIC-MS method required relatively short analysis time (<30 min), in which over 100 glycoforms were distinguished. We suggest that HILIC(-MS) can be a valuable tool in characterizing bioengineering processes aimed at steering protein glycoform expression as well as to check the consistency of product batches.
Topics: Aspergillus niger; Chromatography, Liquid; Glycosylation; Hydrophobic and Hydrophilic Interactions; Lipase; Mannose; Mass Spectrometry
PubMed: 32252907
DOI: 10.1016/j.aca.2020.02.042 -
Bioengineered Dec 2021Raman spectroscopy was applied to an aqueous solution containing D-mannose and D-glucose at a fixed dry matter content. The Raman measurement apparatus was adapted...
Raman spectroscopy was applied to an aqueous solution containing D-mannose and D-glucose at a fixed dry matter content. The Raman measurement apparatus was adapted online at the industrial scale to monitor a bioprocess including an epimerization reaction. Online Raman spectroscopy and deconvolution techniques were successfully applied to monitor in real time the D-mannose and D-glucose concentrations using the Raman shifts at 960 cm and 974 cm respectively. The two anomeric forms, α and β of D-mannose in the pyranose conformation were quantified. In silico analysis of vibrational frequencies and Raman intensities of hydrated structure of D-mannose and D-glucose in the pyranose form for α and β anomers were carried out using a two-step procedure. First molecular dynamics was used to generate the theoretical carbohydrates' structures keeping the experimental dry matter content, then quantum mechanics was used to compute the Raman frequencies and intensities. Computed vibrational frequencies are in satisfactory agreement with the experimental spectra considering a hydration shell approach. Raman intensities are qualitatively in accordance with the experimental data. The interpretation of Raman frequencies and intensities led to acceptable results regarding the current possible structures of D-mannose and D-glucose in aqueous solution. Online Raman spectroscopy coupled with in silico approaches such as quantum mechanics and molecular dynamics methodology is proved to be a valuable tool to quantify the carbohydrates and stereoisomers content in complex aqueous mixtures. This methodology offers a new way to monitor any bioprocesses that encounter aqueous mixtures of D-glucose and D-mannose.
Topics: Glucose; Mannose; Molecular Dynamics Simulation; Spectrum Analysis, Raman; Vibration; Water
PubMed: 34308749
DOI: 10.1080/21655979.2021.1955550