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BMJ (Clinical Research Ed.) Jan 1989
Topics: Constipation; Disaccharides; Humans; Lactulose
PubMed: 2493855
DOI: No ID Found -
Inorganic Chemistry Aug 2023In this study, we have used [H, N] NMR spectroscopy to investigate the interactions of the trinuclear platinum anticancer drug triplatin () (1,0,1 or BBR3464) with...
In this study, we have used [H, N] NMR spectroscopy to investigate the interactions of the trinuclear platinum anticancer drug triplatin () (1,0,1 or BBR3464) with site-specific sulfated and carboxylated disaccharides. Specifically, the disaccharides GlcNS(6)-GlcA () and GlcNS(6)-IdoA(2S) () are useful models of longer-chain glycosaminoglycans (GAGs) such as heparan sulfate (HS). For both the reactions of N with and , equilibrium conditions were achieved more slowly (65 h) compared to the reaction with the monosaccharide GlcNS(6S) (9 h). The data suggest both carboxylate and sulfate binding of disaccharide to the Pt with the sulfato species accounting for <1% of the total species at equilibrium. The rate constant for sulfate displacement of the aqua ligand () is 4 times higher than the analogous rate constant for carboxylate displacement (). There are marked differences in the equilibrium concentrations of the chlorido, aqua, and carboxy-bound species for reactions with the two disaccharides, notably a significantly higher concentration of carboxylate-bound species for , where sulfate-bound species were barely detectable. The trend mirrors that reported for the corresponding dinuclear platinum complex 1,1/, where the rate constant for sulfate displacement of the aqua ligand was 3 times higher than that for acetate. Also similar to what we observed for the reactions of 1,1/ with the simple anions, aquation of the sulfato group is rapid, and the rate constant is 3 orders of magnitude higher than that for displacement of the carboxylate (). Molecular dynamics calculations suggest that extra hydrogen-bonding interactions with the more sulfated disaccharide may prevent or diminish sulfate binding of the triplatin moiety. The overall results suggest that Pt- donor interactions should be considered in any full description of platinum complex cellular chemistry.
Topics: Ligands; Platinum; Heparitin Sulfate; Disaccharides; Sulfates
PubMed: 37552525
DOI: 10.1021/acs.inorgchem.3c01391 -
Molecules (Basel, Switzerland) Apr 2024Rare sugars are known for their ability to suppress postprandial blood glucose levels. Therefore, oligosaccharides and disaccharides derived from rare sugars could...
Rare sugars are known for their ability to suppress postprandial blood glucose levels. Therefore, oligosaccharides and disaccharides derived from rare sugars could potentially serve as functional sweeteners. A disaccharide [α-d-allopyranosyl-(1→2)-β-d-psicofuranoside] mimicking sucrose was synthesized from rare monosaccharides D-allose and D-psicose. Glycosylation using the intermolecular aglycon delivery (IAD) method was employed to selectively form 1,2- α-glycosidic linkages of the allopyranose residues. Moreover, β-selective psicofuranosylation was performed using a psicofuranosyl acceptor with 1,3,4,6-tetra--benzoyl groups. This is the first report on the synthesis of non-reducing disaccharides comprising only rare d-sugars by IAD using protected ketose as a unique acceptor; additionally, this approach is expected to be applicable to the synthesis of functional sweeteners.
Topics: Disaccharides; Sucrose; Glycosylation; Sweetening Agents; Fructose; Glucose
PubMed: 38675593
DOI: 10.3390/molecules29081771 -
The Journal of Biological Chemistry May 2008Recently, a gene cluster involving a phosphorylase specific for lacto-N-biose I (LNB; Galbeta1-3GlcNAc) and galacto-N-biose (GNB; Galbeta1-3GalNAc) has been found in...
Recently, a gene cluster involving a phosphorylase specific for lacto-N-biose I (LNB; Galbeta1-3GlcNAc) and galacto-N-biose (GNB; Galbeta1-3GalNAc) has been found in Bifidobacterium longum. We showed that the solute-binding protein of a putative ATP-binding cassette-type transporter encoded in the cluster crystallizes only in the presence of LNB or GNB, and therefore we named it GNB/LNB-binding protein (GL-BP). Isothermal titration calorimetry measurements revealed that GL-BP specifically binds LNB and GNB with K(d) values of 0.087 and 0.010 microm, respectively, and the binding process is enthalpy-driven. The crystal structures of GL-BP complexed with LNB, GNB, and lacto-N-tetraose (Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc) were determined. The interactions between GL-BP and the disaccharide ligands mainly occurred through water-mediated hydrogen bonds. In comparison with the LNB complex, one additional hydrogen bond was found in the GNB complex. These structural characteristics of ligand binding are in agreement with the thermodynamic properties. The overall structure of GL-BP was similar to that of maltose-binding protein; however, the mode of ligand binding and the thermodynamic properties of these proteins were significantly different.
Topics: Acetylglucosamine; Bacterial Proteins; Bifidobacterium; Calorimetry; Carbohydrate Conformation; Crystallography, X-Ray; Disaccharides; Lectins; Ligands; Models, Molecular; Protein Binding; Protein Structure, Quaternary; Protein Structure, Tertiary; Substrate Specificity; Thermodynamics
PubMed: 18332142
DOI: 10.1074/jbc.M709777200 -
Analytical Chemistry Jun 2009The glycosaminoglycan (GAG) family of biomacromolecules is composed acidic and linear chains of repeating disaccharide units. Quantitative disaccharide composition...
Quantification of heparan sulfate disaccharides using ion-pairing reversed-phase microflow high-performance liquid chromatography with electrospray ionization trap mass spectrometry.
The glycosaminoglycan (GAG) family of biomacromolecules is composed acidic and linear chains of repeating disaccharide units. Quantitative disaccharide composition analysis is essential for the study and characterization of GAGs. Heparan sulfate and heparin consist of multiple disaccharide units and can be well-separated by ion-pairing reversed-phase microflow high-performance liquid chromatography (IPRP-Mf-HPLC). Each disaccharide can be detected and its mass confirmed by electrospray ionization mass spectrometry (ESI-MS). Isotopically enriched disaccharides were prepared chemoenzymatically from a uniformly (13)C,(15)N-labeled N-acetylheparosan (-GlcA(1-->4)GlcNAc-) obtained from the fermentation of E. coli K5. These isotopically enriched disaccharides have identical HPLC retention times and mass spectra as their unlabeled counterparts and were used in liquid chromatography-mass spectrometry (LC-MS) as internal standards. The ratio of intensities between each pair of enriched and nonenriched disaccharides showed a linear relationship as a function of concentration. With the use of these calibration curves, the amount of each disaccharide (> or = 2 ng/disaccharide) could be quantified in four heparan sulfate samples analyzed by this method.
Topics: Animals; Brain Chemistry; Carbon Isotopes; Cattle; Chromatography, High Pressure Liquid; Disaccharides; Escherichia coli; Fermentation; Glycosaminoglycans; Heparitin Sulfate; Liver; Nitrogen Isotopes; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Swine
PubMed: 19402671
DOI: 10.1021/ac9001707 -
The Journal of Physiology Nov 19681. An account is given of the absorption of disaccharides by the small intestine of Rana temporaria, R. pipiens and Bufo vulgaris perfused in vitro through the vascular...
1. An account is given of the absorption of disaccharides by the small intestine of Rana temporaria, R. pipiens and Bufo vulgaris perfused in vitro through the vascular system. Maltase and trehalase activity are found in the intestine of all three species; very small amounts of sucrase are present in the intestine of R. pipiens but there is no evidence for the presence of lactase in any of the animals studied.2. During maltose absorption free glucose appears in the vascular effluent and in the intestinal lumen. Only very small quantities of disaccharide are found in the vascular effluent. The concentration of free glucose in the intestinal lumen during maltose absorption is not high enough to account for the rates of glucose transport observed. The rate of appearance of glucose in the vascular effluent is determined by the concentration of disaccharide in the luminal fluid, and hexose, free in solution in the lumen, is not an obligatory intermediate in the process of disaccharide absorption.3. For R. pipiens more than 90% of the maltase activity in the system is present in the intestinal wall and the rate of maltose hydrolysis by maltase, free in the intestinal lumen, is found to be inadequate to account for the rates of appearance of glucose observed to occur in the lumen and in the vascular effluent. It is not possible to wash away maltase activity from the intestinal wall.4. The kinetic properties of maltase and trehalase acting in situ are of the Michaelis-Menten type; the apparent K(m) is 2 mM for maltase, and 3 mM for trehalase.5. The relationship which exists between the rate of absorption of glucose and the concentration in the luminal fluid of either disaccharide or free glucose is of the Michaelis-Menten type. Expressed in molar units, the apparent K(m) for the glucose transport is about one fifth that of the disaccharidase. The maximum rate of glucose transport observed is less than the maximum rate of disaccharide hydrolysis. In R. pipiens equimolar concentrations in the intestinal lumen of the monomer free glucose, or of the dimer, maltose, yield approximately equal rates of transport of the free hexose.6. It is concluded that in the amphibian, either intestine disaccharide hydrolysis and glucose transport are functions of separate subcellular systems which spatially are very closely related, or that the hydrolysis and transport are different facets of the activity of a common system.
Topics: Animals; Anura; Biological Transport; Disaccharides; Galactosidases; Glucose; Glucosidases; Glycoside Hydrolases; In Vitro Techniques; Intestinal Absorption; Intestine, Small; Kinetics; Maltose
PubMed: 5684031
DOI: 10.1113/jphysiol.1968.sp008643 -
The Biochemical Journal Apr 19791. Preparations of heparin and heparan sulphate were degraded with HNO2. The resulting disaccharides were isolated by gel chromatography, reduced with either NaBH4 or...
1. Preparations of heparin and heparan sulphate were degraded with HNO2. The resulting disaccharides were isolated by gel chromatography, reduced with either NaBH4 or NaB3H4 and were then fractionated into non-sulphated, monosulphated and disulphated species by ion-exchange chromatography or by paper electrophoresis. The non-sulphated disaccharides were separated into two, and the monosulphated disaccharides into three, components by paper chromatography. 2. The uronic acid moieties of the various non- and mono-sulphated disaccharides were identified by means of radioactive labels selectively introduced into uronic acid residues (3H and 14C in D-glucuronic acid, 14C only in L-iduronic acid units) during biosynthesis of the polysaccharide starting material. Labelled uronic acids were also identified by paper chromatography, after liberation from disaccharides by acid hydrolysis or by glucuronidase digestion. Similar procedures, applied to disaccharides treated with NaB3H4, indicated 2,5-anhydro-D-mannitol as reducing terminal unit. On the basis of these results, and the known positions and configurations of the glycosidic linkages in heparin, the two non-sulphated disaccharides were identified as 4-O-(beta-D-glucopyranosyluronic acid)-2,5-anhydro-D-mannitol and 4-O-(alpha-L-idopyranosyluronic acid)-2,5-anhydro-D-mannitol. 3. The three monosulphated [1-3H]anhydromannitol-labelled disaccharides were subjected to Smith degradation or to digestion with homogenates of human skin fibroblasts, and the products were analysed by paper electrophoresis. The results, along with the 1H n.m.r. spectra of the corresponding unlabelled disaccharides, permitted the allocation of O-sulphate groups to various positions in the disaccharides. These were thus identified as 4-O-(beta-D-glucopyranosyl-uronic acid)-2,5-anhydro-D-mannitol 6-sulphate, 4-O-(alpha-L-idopyranosyluronic acid)-2,5-anhydro-D-mannitol 6-sulphate and 4-O-(alpha-L-idopyranosyluronic acid 2-sulphate)-2,5-anhydro-D-mannitol. The last-mentioned disaccharide was found to be a poor substrate for the iduronate sulphatase of human skin fibroblasts, as compared with the disulphated species, 4-O-(alpha-L-idopyranosyluronic acid 2-sulphate)-2,5-anhydro-D-mannitol 6-sulphate. 4. The identified [1-3H]anhydromannitol-labelled disaccharides were used as reference standards in a study of the disaccharide composition of heparins and heparan sulphates. Low N-sulphate contents, most pronounced in the heparin sulphates, were associated with high ratios of mono-O-sulphated/di-O-sulphated (N-sulphated) disaccharide units, and in addition, with relatively large amounts of 2-sulphated L-iduronic acid residues bound to C-4 of N-sulpho-D-glucosamine units lacking O-sulphate substituents.
Topics: Chemical Phenomena; Chemistry; Chromatography, Paper; Disaccharides; Electrophoresis, Paper; Fibroblasts; Glycosaminoglycans; Heparin; Heparitin Sulfate; Magnetic Resonance Spectroscopy; Sulfates
PubMed: 157737
DOI: 10.1042/bj1790077 -
Journal of the American Chemical Society Mar 2012The disaccharide motif fucose-α(1-2)-galactose (Fucα(1-2)Gal) is involved in many important physiological processes, such as learning and memory, inflammation, asthma,...
The disaccharide motif fucose-α(1-2)-galactose (Fucα(1-2)Gal) is involved in many important physiological processes, such as learning and memory, inflammation, asthma, and tumorigenesis. However, the size and structural complexity of Fucα(1-2)Gal-containing glycans have posed a significant challenge to their detection. We report a new chemoenzymatic strategy for the rapid, sensitive detection of Fucα(1-2)Gal glycans. We demonstrate that the approach is highly selective for the Fucα(1-2)Gal motif, detects a variety of complex glycans and glycoproteins, and can be used to profile the relative abundance of the motif on live cells, discriminating malignant from normal cells. This approach represents a new potential strategy for biomarker detection and expands the technologies available for understanding the roles of this important class of carbohydrates in physiology and disease.
Topics: Biomarkers; Disaccharides; Enzymes; Molecular Probes; Polysaccharides
PubMed: 22339094
DOI: 10.1021/ja211312u -
Plant Physiology Jan 2017Successful fertilization in flowering plants depends on the precise directional growth control of pollen tube through the female pistil tissue toward the female...
Successful fertilization in flowering plants depends on the precise directional growth control of pollen tube through the female pistil tissue toward the female gametophyte contained in the ovule for delivery of nonmotile sperm cells. Cys-rich peptides LUREs secreted from the synergid cells on either side of the egg cell act as ovular attractants of pollen tubes. Competency control by the pistil is crucial for the response of pollen tubes to these ovular attractants. We recently reported that ovular 4-O-methyl-glucuronosyl arabinogalactan (AMOR) induces competency of the pollen tube to respond to ovular attractant LURE peptides in Torenia fournieri. The beta isomer of the terminal disaccharide 4-O-methyl-glucuronosyl galactose was essential and sufficient for the competency induction. However, critical and noncritical structures in the disaccharide have not been dissected deeply. Herein, we report the synthesis of new AMOR analogs and the structure-activity relationships for AMOR activity in the presence of these synthesized analogs. Removal of 4-O-methyl group or -COOH from the glucuronosyl residue of the disaccharide dramatically reduces AMOR activity. The pyranose backbone of the second sugar of disaccharide is essential for the activity but not hydroxy groups. The role of beta isomer of the disaccharide 4-Me-GlcA-β(1,6)-Gal is very specific for competency control, as there was no difference in effect among the sugar analogs tested for pollen germination. This study represents the first structure-activity relationship study, to our knowledge, of a sugar molecule involved in plant reproduction, which opens a way for modification of the molecule without loss of activity.
Topics: Disaccharides; Galactans; Germination; Glycosylation; Lamiaceae; Ovule; Pollen Tube; Structure-Activity Relationship
PubMed: 27913739
DOI: 10.1104/pp.16.01655 -
Journal of Chromatography. A Feb 2012Glycosaminoglycans are a family of polysaccharides widely distributed in all eukaryotic cells. These polyanionic, linear chain polysaccharides are composed of repeating...
Glycosaminoglycans are a family of polysaccharides widely distributed in all eukaryotic cells. These polyanionic, linear chain polysaccharides are composed of repeating disaccharide units that are often differentially substituted with sulfo groups. The diversity of glycosaminoglycan structures in cells, tissues and among different organisms reflect their functional an evolutionary importance. Glycosaminoglycan composition and structure also changes in development, aging and in disease progression, making their accurate and reliable analysis a critical, albeit, challenging endeavor. Quantitative disaccharide compositional analysis is one of the primary ways to characterize glycosaminoglycan composition and structure and has a direct relationship with glycosaminoglycan biological functions. In this study, glycosaminoglycan disaccharides, prepared from heparan sulfate/heparin, chondroitin sulfate/dermatan sulfate and neutral hyaluronic acid using multiple polysaccharide lyases, were fluorescently labeled with 2-aminoacridone, fractionated into 17 well-resolved components by reverse-phase ultra-performance liquid chromatography, and analyzed by electrospray ionization mass spectrometry. This analysis was successfully applied to cell, tissue, and biological fluid samples for the picomole level detection of glycosaminoglycan composition and structure.
Topics: Animals; CHO Cells; Camelus; Chromatography, High Pressure Liquid; Cricetinae; Cricetulus; Disaccharides; Glycosaminoglycans; Liver; Spectrometry, Mass, Electrospray Ionization
PubMed: 22236563
DOI: 10.1016/j.chroma.2011.12.063