Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DISACCHARIDES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed2002

Analysis of glycosaminoglycan-derived disaccharides in biologic samples by capillary electrophoresis and protocol for sequencing glycosaminoglycans.

Glycosaminoglycans are biologically significant carbohydrates which either as free chains (hyaluronan) or constituents of proteoglycans (chondroitin/dermatan sulfates, heparin, heparan sulfate and keratan sulfate) participate and regulate several cellular events and (patho)physiological processes. Capillary electrophoresis, due to its high resolving power and sensitivity, has been successfully used for the analysis of glycosaminoglycans. Determination of compositional characteristics, such as disaccharide sulfation pattern, is a useful prerequisite for elucidating the interactions of glycosaminoglycans with matrix effective molecules and, therefore, essential in understanding the biological functions of proteoglycans. The interest in the field of characterization of such biologically important carbohydrates is soaring and advances in this field will signal a new revolution in the area of glycomics equivalent to that of genomics and proteomics. This review focuses on the capillary electrophoresis methods used to determine the disaccharide pattern of glycosaminoglycans in various biologic samples as well as advances in the sequence analysis of glycosaminoglycans using both chromatographic and electrophoretic techniques.

Carbohydrate Sequence↗
PubMed1977

Analysis of hexosaminitol-containing disaccharide alditols from rat brain glycoproteins and gangliosides as O-trimethylsilyl derivatives by gas chromatography mass spectrometry.

The O-trimethylsilyl derivatives of five reference disaccharide alditols composed of a N-acetylhexosaminitol substituted at C-3, C-4 or C-6 with a hexose moiety were studied by gas chromatography mass spectrometry. The data were used in the determination of the linkage in disaccharide alditols derived from rat brain glycoproteins and gangliosides. The O-glycosidically linked carbohydrate units of brain glycoproteins contained two oligosaccharides, alpha-galactosyl-(1 leads to 3)-N-acetylgalactosaminitol and beta-galactosyl-(1 leads to 3)-N-acetylgalactosaminitol, whereas only the latter was obtained from brain gangliosides after partial acid hydrolysis and reduction.

Animals↗
PubMed1980

The use of collisional activation spectra in the discrimination of stereoisomeric permethylated disaccharides.

Collisional activation spectra of quasimolecular ions generated by chemical ionization can be used for the discrimination of stereoisomeric permethylated disaccharides. The best results have been obtained by using ammonia and trimethylamine as reagent gases. In the case of trimethylamine the presence of water seems to play an important role in order to obtain distinctive collisional activation spectra. The structural information obtained with the chemical ionization gases mentioned is complementary. A flow chart is presented for the identification of an unknown permethylated disaccharide.

Ammonia↗
PubMed2004

Disaccharide mimetics of the aminoglycoside antibiotic neamine.

A highly convergent approach has been employed for the facile synthesis of a library of 24 disaccharides that are alpha(1-3), beta(1-3), alpha(1-4), or beta(1-4) linked and contain 2-4 amino groups. Fourier-transformation ion cyclotron resonance mass spectrometry (FT-ICR MS) has been used to determine dissociation constant (Kd) values for the binding of the disaccharides to a prototypical fragment of 16S ribosomal RNA. Several derivatives bound with affinities similar to that of neamine. Structure-activity relationships have revealed the substitution pattern that is important for high-affinity binding. The compounds described here are unique lead compounds for the design of novel aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1998

Separation of disaccharides by affinity capillary electrophoresis in lectin-containing electrophoretic solutions.

Separation of the 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives of simple disaccharides (maltose, cellobiose, gentiobiose, lactose, and melibiose) by affinity capillary electrophoresis was investigated using lectin-containing neutral phosphate buffers, filled in a linear polyacrylamide-coated capillary. When Lens culinaris agglutinin (LCA) was added, the derivatives of glucobioses were retarded with varying magnitudes depending on the amount of LCA and were well separated from each other and from galactosyl glucose under optimized conditions. Addition of Ricinus communis 60 kDa agglutinin (RCA60) to the phosphate buffer gave a different migration profile, in which the derivatives of galactosyl glucoses were more retarded than those of glucobioses. However, addition of either lectin did not accomplish complete separation of the derivatives of all these disaccharides even under optimum conditions. The addition of two kinds of lectins in appropriate proportions improved separation. Thus, the binary system composed of LCA and RCA60, as well as LCA and soybean agglutinin from Glycine max (SBA), gave better separation of these derivatives, giving peak tops for all derivatives.

Antipyrine↗
PubMed2003

Sensory neuropathy with monoclonal IgM binding to a trisulfated heparin disaccharide.

We studied clinical and serological features of five patients with polyneuropathy and serum immunoglobulin M (IgM) binding to the trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS), the most abundant disaccharide component of heparin oligosaccharides. The patients all had painful, predominantly sensory polyneuropathies. Sensory loss was distal and panmodal. Electrophysiological and pathological studies were consistent with axonal loss, especially of unmyelinated axons. Immunohistochemistry showed IgM and kappa light chains deposited around the rim of intermediate-sized veins in the perimysium and epineurium. Serum IgM binding to TS-HDS was selective, present in high titer (>12,000), and limited to kappa light chains. We conclude that TS-HDS is a newly identified target carbohydrate antigen of some IgM M-proteins. Monoclonal IgM binding to TS-HDS is associated with a painful, predominantly sensory, polyneuropathy syndrome with axonal loss and deposition of IgM in veins. The role of IgM binding to TS-HDS in the pathogenesis of the neuropathy remains to be determined.

Aged↗
PubMed1996

Tumor marker disaccharide D-Gal-beta 1, 3-GalNAc complexed to heat-labile enterotoxin from Escherichia coli.

Heat-labile enterotoxin (LT) is part of the cholera toxin (CT) family and consists of a catalytic A subunit and a B pentamer that serves to recognize the oligosaccharide part of the GM1 ganglioside receptor. We report here the crystal structure of heat-labile enterotoxin in complex with the disaccharide portion of the Thomsen-Friedenreich (T-antigen) tumor marker. The toxin:carbohydrate complex is determined to 2.13 A resolution, yielding an R-factor of 18.5%. The T-antigen disaccharide, D-Gal-beta 1,3-GalNAc-Ser/Thr, is present in more than 85% of human carcinomas and monitoring its autoimmune response is used for the early detection of tumors. Insight into the molecular recognition of this tumor antigen by sugar binding proteins can benefit the development of a diagnostic tool for human carcinomas as well as a T-antigen directed anticancer drug delivery system.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2004

Antiallergic activity of a disaccharide isolated from Sanguisorba officinalis.

The antiallergic activity of the natural disaccharide, 5-O-alpha-D-(3-C-hydroxymethyl)lyxofuranosyl-beta-D-(2-C-hydroxymethyl)arabinofuranose was evaluated using both in vivo and in vitro experimental models. Intravenously administered compound inhibited the passive cutaneous anaphylaxis response in rats in a dose-dependent manner (ED(50) = 9.6 mg/kg). The compound inhibited histamine release evoked by both compound 48/80 and calcium ionophore A23187 in rat peritoneal mast cells indicating that mast cell stabilization is the major mechanism of action for its antiallergic activity. In passively sensitized isolated guinea-pig hearts, an in vitro anaphylaxis model in which histamine release plays a key role for functional deterioration, the compound markedly diminished both coronary flow reduction and histamine release on challenge to the antigen. These data demonstrate that this antiallergic natural disaccharide exerts its effect via inhibition of mast cell mediator release.

Animals↗
PubMed1991

Determination of the glycosidic linkage in peracetylated disaccharides comprised of D-glucopyranose units by use of desorption electron-ionization mass spectrometry.

An oxonium ion at m/z317 is present in the desorption electron ionization and ammonia desorption chemical ionization mass spectra of peracetylated disaccharides, comprised of glucopyranose units linked (1-->2), (1-->3), (1-->4) and (1-->6), but is absent in the spectra of the (1-->1)-linked isomer. The ion at m/z317, which is derived from the reducing moiety, has an O-formyl group at the position of linkage to the non-reducing moiety, and O-acetyl groups at each of the remaining positions. The isomeric monoformyl, triacetyl oxonium ions (at m/z317), derived from the (1-->2)-, (1-->3)-, (1-->4)- and (1-->6)-linked disaccharides, give distinctly different mass-analysed ion kinetic energy spectra, thereby enabling the linkage position to be assigned unambiguously.

Acetylation↗
PubMed1999

Microanalysis of glycosaminoglycan-derived oligosaccharides labeled with a fluorophore 2-aminobenzamide by high-performance liquid chromatography: application to disaccharide composition analysis and exosequencing of oligosaccharides.

A series of disaccharides derived from chondroitin sulfate and heparin/heparan sulfate were derivatized at their reducing ends with a fluorophore 2-aminobenzamide to develop a sensitive microanalytical method for glycosaminoglycans. The resulting labeled compounds derived from chondroitin sulfate or heparin/heparan sulfate were well-separated and quantified by HPLC equipped with a fluorescence detector. The detection limit was a low picomole level. This method was applied to the analysis of the disaccharide composition of tetra- and hexasaccharides derived from chondroitin sulfate and heparin/heparan sulfate as well as these glycosaminoglycan polysaccharides. The method was also successfully applied to the exosequencing of chondrohexasaccharides, where the fluorophore-labeled oligosaccharides were degraded exolytically from the nonreducing ends using bacterial eliminases. The resultant labeled fragments were identified by HPLC.

Carbohydrate Sequence↗
PubMed1999

Disaccharide analysis and molecular mass determination to microgram level of single sulfated glycosaminoglycan species in mixtures following agarose-gel electrophoresis.

The separation of sulfated glycosaminoglycans in mixtures by agarose-gel electrophoresis and the recovery of single polysaccharide bands has been applied to the characterization of polysaccharides extracted from tissues without previous purification of single species. Sulfated glycosaminoglycans, heparin with its two components, slow-moving and fast-moving, heparan sulfate, dermatan sulfate, and chondroitin sulfate, were separated to microgram level by conventional agarose-gel electrophoresis. After their separation, they were fixed in the agarose-gel matrix by precipitation in a cetyltrimethylammonium bromide solution, making them visible on a dark background. After recovery of gel containing the fixed bands, high temperatures (90 degrees C for 15 min) were necessary to dissolve the gel matrix, and a solution of NaCl (3 M) was used to release sulfated polysaccharides from the complex with cetyltrimethylammonium. After precipitation of glycosaminoglycans in the presence of ethanol, the recovery of slow-moving heparin, fast-moving heparin, heparan sulfate, dermatan sulfate, and chondroitin sulfate was from 1 to 10 microg, with a percentage greater than 45% and a purity above 90%. Sulfated glycosaminoglycans in mixtures recovered from gel matrix as single species were evaluated for purity and characterized for unsaturated disaccharides after treatment with bacterial lyases (heparinases for heparin and heparan sulfate samples, and chondroitinases for dermatan sulfate and chondroitin sulfate) and molecular mass. Bovine lung and heart Glycosaminoglycans were extracted and separated into single species by agarose-gel electrophoresis and recovered from gel matrix after treatment in cetyltrimethylammonium solution. Unsaturated disaccharides pattern, the sulfate to carboxyl ratio, and the molecular mass of each single polysaccharide species were determined.

Animals↗
PubMed2000

Hyaluronic acid and chondroitin sulfate unsaturated disaccharides analysis by high-performance liquid chromatography and fluorimetric detection with dansylhydrazine.

A system capable of resolving all the known unsaturated nonsulfated, mono- and disulfated disaccharides derived from chondroitin sulfate samples, dermatan sulfate, and hyaluronic acid after their derivatization with dansylhydrazine and separation by HPLC and fluorimetric detection is reported. This method was found superior to others in that unsaturated disaccharides can be separated with good resolution in about 50 min in an isocratic solvent with a sensitivity greater than about 50 pmol (approx 20-30 ng) and linearity from 50 to 500 pmol. The system was applied to the analysis of various chondroitin sulfate samples, including highly sulfated species and dermatan sulfate, and also to a defructosylated polysaccharide with a chondroitin backbone purified from Escherichia coli U1-41. Excellent agreement was obtained with traditional compositional analysis performed by anion-exchange HPLC separation and UV absorption at 230 nm.

Calibration↗
PubMed1995

Synthesis of three hetero disaccharides, 4-O-beta-glucopyranosyl-6-deoxy-D-glucose, 4-O-beta-D-glucopyranosyl-D-mannosamine, and 4-O-beta-D-glucopyranosyl-D-mannose, and confirmation of their structures by C-13 NMR and MS.

The three disaccharides, 4-O-beta-D-glucopyranosyl-6-deoxy-D-glucose (Glc-6-deoxy-Glc), 4-O-beta-D-glucopyranosyl-D-mannosamine (Glc-ManN), 4-O-beta-D-glucopyranosyl-D-mannose (Glc-Man), were synthesized from equimolar amounts of 6-deoxy-glucose and alpha-D-glucose-1-phosphate (G-1-P), D-mannosamine and alpha-D-glucose-1-phosphate (G-1-P), and D-mannose and alpha-D-glucose-1-phosphate (G-1-P), respectively, using cellobiose phosphorylase from Cellvibrio gilvus. The yields were 60%, 10% and 50% based on the initial amounts of 6-deoxy-D-glucose, D-mannosamine and D-mannose, respectively. The structures of disaccharides were confirmed by NMR and mass spectroscopy analysis.

Amino Sugars↗
PubMed1991

Data bank of three-dimensional structures of disaccharides: Part II, N-acetyllactosaminic type N-glycans. Comparison with the crystal structure of a biantennary octasaccharide.

Conformational energy maps and descriptions of structures at the local minima are presented for the following fragments found in N-acetyllactosaminic type glycans of N-glycoproteins: GlcNAc beta(1-2)Man, GlcNAc beta(1-4)Man, GlcNAc beta(1-6)Man, Gal beta(1-4)GlcNAc, GlcNAc beta(1-3)Gal, Fuc alpha(1-6)GlcNAc, Fuc alpha(1-3)GlcNAc, Xyl beta(1-2)Man, Gal beta(1-3)GlcNAc and GlcNAc beta(1-6)Gal. These results are the second part of a data bank on glycoprotein moieties; five disaccharides found in oligomannose type N-glycans were analysed earlier (Imberty et al., 1990, Glycoconjugate J 7:27-54). In the present study, three to seven minima are found for each dimer. Conformations of disaccharide fragments found in the crystal structure of the complex of a biantennary octasaccharide with Lathyrus ochrus lectin are plotted on these energy maps. While the observed conformations are at predicted minima, they are not always at the minimum predicted to have the lowest energy. Further, not all observed conformations are stabilized by the exo-anomeric effect. We conclude that these oligosaccharides are highly flexible.

Carbohydrate Conformation↗
PubMed1989

Intestinal disaccharidases assessed in congenital asucrasia by differential urinary disaccharide excretion.

A patient with congenital asucrasia was investigated using in vivo differential urinary disaccharide excretion. Impaired hydrolysis of sucrose and isomaltose, but normal lactase activity, were demonstrated and confirmed by in vitro estimation. The technique of differential disaccharide excretion can now be used to assess three disaccharidases simultaneously, in vivo, including isomaltase.

Adult↗
PubMed1989

Proximal small intestinal mucosal injury. Maintenance of glucose and glucose polymer absorption, attenuation of disaccharide absorption.

The effect of chronic intragastric infusion of hypertonic mannitol on small intestinal mucosal structure and function was studied in adult rats. Animals were gavage-fed 20% mannitol (1300 mosm) at a dose of 5 ml/100 g body weight daily for seven days. Control animals were gavage-fed tap water on the same schedule. On day 8, the animals were anesthetized, the duodenum cannulated, and a test sugar (glucose, glucose polymer, lactose, sucrose, or maltose) was infused at a dose of 0.5 g/kg body weight in 2.5 ml distilled water over less than 1 min. Portal vein glucose was measured at 30-min intervals from 0 to 120 min. Mannitol treatment resulted in histologic and biochemical alterations (reduced lactase, sucrase, maltase) limited to the proximal small intestine compared to the control group. The absorption of glucose and glucose polymers was similar in mannitol-treated and control animals. In contrast, digestion and absorption of lactose, sucrose, and maltose was significantly diminished in mannitol-treated animals when compared to controls. No changes in permeability to polyethylene glycol 4000 or Na+-coupled glucose transport were observed in mannitol-treated animals compared to controls. These data suggest that when the intestinal mucosa is exposed to hyperosmolar loads that the digestive capacity for disaccharides is suppressed more than its glucose absorptive capacities. Furthermore, glucose oligomers may be more readily digested and absorbed than disaccharides, in this setting, due, in part, to the proximal injury and less pronounced proximal-distal gradient for glucoamylase than other brush-border carbohydrases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Blocking of human anti-pig xenoantibodies by soluble GAL alpha 1-3Gal and Gal alpha 1-2Gal disaccharides; studies in a pig kidney in vitro perfusion model.

Depletion of anti-pig xenoantibodies reduces cell cytotoxicity of human serum to pig endothelial cells and lymphocytes. The aim of this study was to test, in a pig kidney xenoperfusion model, the ability of soluble alpha Gal terminated disaccharides to prevent the hyperacute rejection process in an organ. Porcine kidneys were perfused with whole human blood lacking saccharide and blood supplemented with Gal alpha 1-3GAL, Gal alpha 1-2Gal and lactose. Parameters evaluated were, urine production, renal blood flow, vascular resistance, renal clearance, blood cell counts, xenoantibody titers, complement activation and histopathology. The blood flow was higher in the Gal alpha 1-3Gal (155 +/- 31 ml/min x 100 g-1 kidney tissue) group compared to Gal alpha 1-2Gal (138 +/- 16), lactose (92 +/- 78) and controls (69 +/- 16), When calculated as percent of the blood flow value at 1 min, the blood flow at 30 min was 157% for the Gal alpha 1-3Gal and for 187% the Gal alpha 1-2Gal. The corresponding values for the lactose and control groups were 102% and 74%, respectively. Urine production in the lactose/control groups was lower (0.7 ml/min x 100 g-1 kidney tissue) compared to Gal alpha 1-3Gal (3.0) and Gal alpha 1-2Gal (3.7). Urine sodium excretion was reduced in the lactose/control groups, compared to the Gal alpha alpha 1-groups during the perfusions. An increase in urine potassium excretion was found in the Gal alpha alpha 1-groups while a reduction occurred in the lactose/control experiments. An initial 40-50% reduction in platelet count was observed in all groups while the leukocyte count showed a continuous decrease. Immunohistochemistry revealed less deposition of IgM, IgG, C3 and C1 q in the Gal alpha alpha 1-saccharide groups compared to the lactose/control groups. Soluble Gal alpha a1-disaccharides improved both functional and histological parameters. However, significant pathological changes were still present indicating that this approach to inhibit HAR must be used in combination with additional therapeutic approaches such as solid phase xenoantibody immunoadsorption and blocking of complement activation.

Animals↗
PubMed2001

Pharmacokinetics of MEN-10755, a novel anthracycline disaccharide analogue, in two phase I studies in adults with advanced solid tumours.

The doxorubicin analogue MEN-10755 has been identified as a compound with promising antitumour activity based on structure-activity studies of a new series of anthracycline disaccharides. The high antitumour activity of MEN-10755 in human tumour xenografts, including doxorubicin-resistant xenografts, and its unique pharmacological and biological properties made this novel disaccharide analogue an interesting candidate for clinical evaluation. Two pharmacokinetic phase I studies with different dosing schedules were performed in adults with solid refractory malignancies. The pharmacokinetics of MEN-10755 were studied after a 15-min i.v. infusion given once every 3 weeks or once every week for 3 weeks followed by 1 week rest. Plasma and urine levels of MEN-10755 were measured by HPLC with fluorescent detection. It was possible to combine the pharmacokinetic results of the two studies because there was no accumulation of MEN-10755 before the next infusion of MEN-10755 in the weekly study with 1 week rest. The administered dose levels on day 1 in this study were all in the lower range from the 3-weekly study. The postinfusion plasma kinetics of MEN-10755 were best described by a triexponential model. The plasma peak levels (Cmax) of MEN-10755 showed a linear relationship with the administered dose. Peak plasma MEN-10755 levels ranged between 474 and 21,587 microg/l. The mean elimination half-life (T(1/2gamma)) was 20.7+/-9.0 h. The AUC(0-infinity) was proportional to the administered dose. The mean plasma clearance of MEN-10755 was 6.0+/-2.2 l/h per m2 with a mean volume of distribution (Vss) of 95.6+/-43.4 l/m2. The mean renal excretion of unchanged drug within 24 h was 4.3+/-1.8%. Compared to epirubicin and doxorubicin, the pharmacokinetics of MEN-10755 were characterized by an approximately twofold shorter terminal half-life, a much lower total plasma clearance and a much smaller volume of distribution.

Adult↗