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PubMed1994

Disaccharide analysis of the skin glycosaminoglycans in patients with Werner's syndrome.

The disaccharide content of the chondroitinase-digestible glycosaminoglycans (GAGs) extracted from 6-mm skin punch biopsies from the atrophic and sclerotic skin of two patients with Werner's syndrome (WS) were determined using high-performance liquid chromatography after 1-phenyl-3-methyl-5-pyrazolone labelling. The total amount of main disaccharides was significantly decreased in the atrophic lesions of WS. In the atrophic forearm skin, the decrease in the main disaccharide unit of hyaluronic acid, delta Di-HA, and the increase in the ratio of the main disaccharide unit of dermatan sulphate, delta Di-4S, to delta Di-HA were significant vs. normal control (P < 0.01 and 0.05, respectively). The sclerotic skin showed an increase in delta Di-4S (DS) (P < 0.05) and a decrease in delta Di-HA (P < 0.02) compared with normal controls, as well as a significantly higher ratio of delta Di-4S (DS)/delta Di-HA compared with normal controls (P < 0.0002) and systemic sclerosis patients (SSc; P < 0.02). No other statistical difference was found in the amount of each main disaccharide unit between the sclerotic skin of WS and SSc. Histological examination revealed that the atrophic skin showed thinning of the dermis with a slight increase of fine collagen bundles, whereas the sclerotic skin demonstrated a thickened dermis with prominent deposition of fine collagen bundles in the deep dermis. In SSc, thickening of the whole dermis, composed of hyalinized or swollen collagen bundles, was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Structure of the disaccharide chain of galactosyl-N-acetylgalactosaminyl-protein synthesized in vitro.

In order to obtain a [14C]galactosyl-N-acetylgalactosaminyl-protein which would be useful as an acceptor in studies on the specificity of glycosyltransferases, a porcine submaxillary gland microsomal galactosyltransferase preparation was used for the galactosylation in vitro of N-acetylgalactosaminyl-protein (desialylated ovine submaxillary mucin). The newly formed oligosaccharide unit was obtained as a reduced disaccharide after alkaline borohydride treatment of the [14C]galactosyl-N-acetylgalactosaminyl-protein product and as glycopeptides by proteolytic digestion of the glycoprotein. The reduced disaccharide consisted of equimolar amounts of galactose and N-acetylgalactosaminitol and was characterized by thin-layer chromatography, high-voltage electrophoresis and gas-liquid chromatography. Periodate oxidation studies on the reduced disaccharide revealed that [14C]galactose was linked to position C-3 on the N-acetylgalactosaminyl residue. Digestion of the reduced disaccharide and the glycopeptides with galactosidases gave equivocal results as to the anomeric configuration of the [14C]galactose residue. Nuclear magnetic resonance of the reduced disaccharide, however, definitely indicated that the configuration was beta. The specificity of the porcine submaxillary gland galactosyltransferase thus can be defined as a uridine diphosphogalactose: alpha-D-N-acetylgalactosaminyl-protein beta 1 leads to 3 transferase activity.

Acetylgalactosamine↗
PubMed1971

Relationships between disaccharide hydrolysis and sugar transport in amphibian small intestine.

1. A study is described of the relationships which exist between disaccharide hydrolysis and glucose transport in the small intestine of Rana pipiens and Bufo vulgaris. The experiments were undertaken on the intestine perfused in vitro through the vascular system and with fluid circulating through the intestinal lumen. For this system it was found that, with [U-(14)C]glucose in the intestinal lumen, the apparent specific activity of the glucose appearing in the vascular effluent was not significantly different from that in the lumen.2. Changes of ionic composition of vascular and luminal fluids, and the presence of phloridzin or strophanthin, had little effect upon the maltase activity in situ in R. pipiens, although this activity was somewhat reduced when the sodium of the intestinal lumen was replaced by lithium. In contrast, in all cases a marked reduction was found in the rate of glucose translocation in the vascular effluent.3. With Tris substituted for the luminal sodium, there was evidence of a competitive inhibition of the maltase activity in situ by the buffer cation. At the same time, the rate of glucose translocation into the vascular effluent was but little affected and there was an apparent increase in the efficiency with which the cellular systems responsible for the translocation were able to capture the glucose liberated.4. It was found that competition for transepithelial translocation occurred between the glucose initially present in the intestinal lumen, and glucose derived from either maltose or trehalose. There was no evidence for competition for hydrolysis between maltose and trehalose, yet the glucose units derived from these two disaccharides competed with each other for translocation.5. The significance is discussed of the finding that it is possible to dissociate the processes of disaccharide hydrolysis from those underlying the translocation of hexose units into the vascular effluent. It is suggested that monosaccharide units released by the hydrolysis of disaccharide molecules have access to a pool of glucose which is equally accessible to glucose free in the intestinal lumen. It is also suggested that the rate of transport of glucose from the pool into the vascular effluent (i.e. glucose translocation) is determined by the concentration of glucose within the pool. From consideration of the properties of a model operating upon these principles, it is possible to predict the relative contribution of disaccharides and monosaccharides in the intestinal lumen to the glucose appearing in the vascular effluent. The experimentally determined contributions of the two sources are very similar to those predicted from the model. The implications of possible sites for the postulated pool are discussed.

Animals↗
PubMed1977

Specificity of the disaccharide effect in the rat.

Male rats were starved and refed diets containing 40% disaccharides (maltose, trehalose, sucrose, turanose), trisaccharide (melezitose), starch, or the monosaccharide equivalents. Responses of hepatic glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), fatty acid synthetase (FAS), and total liver lipid (TLL) or changes in concentration of portal blood total carbohydrate and fructose were determined following refeeding of the different carbohydrate diets. Maltose, trehalose, sucrose, and turanose refeeding resulted in G6PD and ME responses which were higher than the responses to their component monosaccharides (disaccharide effect). Starch refeeding decreased the responses of G6PD, ME, and FAS when compared to refeeding of glucose. Refeeding diets containing fructose (sucrose, turanose, melezitose, and monosaccharide equivalents containing fructose) increased the responses of G6PD, ME, FAS, and TLL. No correlation between portal blood carbohydrate concentration and hepatic enzyme levels could be demonstrated. It is concluded that readily digestible disaccharides produce an effect which is greater than the effect produced by their monosaccharide equivalents. If these disaccharide configurations are fed as part of a trisaccharide or polysaccharide, the disaccharide effect is no longer discernible.

Animals↗
PubMed2005

Detection and quantification of sulfated disaccharides from keratan sulfate and chondroitin/dermatan sulfate during chick corneal development by ESI-MS/MS.

PURPOSE: To identify and quantify changes in keratan sulfate (KS) and chondroitin/dermatan sulfate (CS/DS) sulfated disaccharides in the developing chick cornea using electrospray ionization tandem mass spectrometry (ESI-MS/MS). METHODS: Cryostat sections of fresh nonfixed corneas were obtained from White Leghorn embryonic day (E)8 to E20 chicks, and from 4- and 70-week-old chickens. Tissue sections on glass slides were incubated with selected glycosidase enzymes. Digest solutions were analyzed directly by ESI-MS/MS. RESULTS: The concentration of KS monosulfated disaccharide (MSD) Gal-beta-1,4-GlcNAc(6S) in E8 cornea equaled that at E20, declined to its lowest level by E10, increased to a second peak by E14, decreased to a second low by E18, peaked again by E20, and remained high in adult corneas. A similar concentration profile was observed for KS disulfated disaccharide (DSD) Gal(6S)-beta-1,4-GlcNAc(6S), and thus also for total sulfated KS disaccharides. The molar percent of DSD was higher than that of MSD from E8 to E18, equivalent at E20, and less than that of MSD in adult corneas. In contrast, total concentration of CS/DS Deltadi-4S plus Deltadi-6S decreases as development progresses and is lowest in adult corneas. Concentration and molar percent of Deltadi-6S is highest at E8, then decreases through development as the concentration and molar percent of Deltadi-4S increases from E8 and exceeds that of Deltadi-6S after E14. CONCLUSIONS: New, rapid, direct chemical analysis of extracellular matrix components obtained from sections from embryonic and adult chick corneas reveals heretofore undetected changes in sulfation characteristics of KS and CS/DS disaccharides during corneal development.

Animals↗
PubMedDate not supplied

Binding of T-antigen disaccharides to Artocarpus hirsuta lectin and jacalin are energetically different.

The thermodynamics of binding of Me-alpha(-GalNAc, Gal-beta-1-3GalNAc-alpha-O-Me (T-antigen-alpha), Gal-beta-1-3GalNAc and Gal-alpha-1-6Glc (mellibiose) to Artocarpus hirsuta lectin was studied using fluorescence spectroscopy. The binding affinities of the saccharides are in the order Gal-beta-1-3GalNAc-alpha-O-Me > Me-alpha-GalNAc > Me-alpha-Gal > Gal-beta-1-3GalNAc > Gal-alpha-1-6Glc. The binding affinities were comparable to those for jacalin. However, binding of the saccharides to the A. hirsuta lectin was not affected as strongly by temperature as observed in jacalin and the trend was found to be reversed. Values for AH and AS were found to be positive in A. hirsuta lectin-disaccharide binding despite similar binding affinities. Thus, with 99% structural and 96% sequence homology, with similar sugar specificity and affinity, the energetics of the disaccharide binding of the two lectins seem to be different. Me-alpha-GalNAc binding to A. hirsuta lectin is enthalpically driven, because the association constant decreases with increasing temperature. However, the binding of the T-antigen disaccharides and mellibiose disaccharides to the lectin is entropically driven. The difference in the molecular associations in the packing and variation of the C-terminal length of the beta chain of the A. hirsuta lectin could be reflected in the different disaccharide binding energetics.

Antigens, Viral, Tumor↗
PubMed1976

Interpretation of disaccharide-dependent electrical potential differences in the small intestine.

The nature of maltose- and trehalose-induced electrical potential increments across everted small intestines of toads were investigated. A Michaelis-Menten-like relation was seen between the amplitude of PD increments (deltaPD) and the mucosal concentration of disaccharides over a wide range of concentration, but, at a higher concentration range, Lineweaver-Burk type plot of data always deviated from the linear line for the low and moderate concentration range. The extrapolation of the linear segment of the plots intercepted the ordinate at the same point as that of the line for the glucose-induced potential increments. Both the disaccharide- and the glucose-evoked potentials were not additive and were equally sensitive to phlorizin. Tris depressed the disaccharide-evoked potentials to about the same extent as that of inhibition of enzyme activities. The amplitude and time course of the disaccharide-induced potentials, however, could not be accounted for by the mucosal concentration of liberated glucose. These qualitative and quantitative characteristics were explained properly on the basis of a simple well-type local pool for liberated glucose assumed to exist at the brush border. In conclusion, a close functional linkage between brush border membrane disaccharidase activities and the electrogenic hexose transport is well reflected in the disaccharide-evoked potentials in the small intestine.

Animals↗
PubMed2003

A disaccharide precursor of sialyl Lewis X inhibits metastatic potential of tumor cells.

Clustered presentation of sialyl Lewis X (sLe(X)) on tumor cell mucins is thought to facilitate metastasis through binding to selectin adhesion receptors expressed on platelets, leukocytes and endothelial cells. Thus, interfering with sLe(X) assembly might provide a chemotherapeutic method for treating metastatic disease. Prior studies have shown that peracetylated disaccharides can act in cells as substrates for the assembly of oligosaccharides related to sLe(X) synthesis, and the assembly of oligosaccharides on the disaccharides diverts the assembly of sLe(X) from endogenous cell surface glycoconjugates. Here, we show that treatment of cultured human adenocarcinoma cells with micromolar concentrations of the peracetylated disaccharide, (Ac)(6)GlcNAcbeta1,3Galbeta-O-naphthalenemethanol (AcGnG-NM) reduces the expression of sLe(X) and diminishes binding in vitro to selectin-coated dishes, thrombin-activated platelets, and tumor necrosis factor alpha-activated endothelial cells. Altering glycosylation in this way significantly reduced the ability of tumor cells to distribute to the lungs of wild-type mice over a 3-h period after i.v. injection. No significant difference in biodistribution was noted after the injection of AcGnG-NM-treated tumor cells into P-selectin deficient mice, although the extent of lung seeding was reduced compared with that in wild-type mice. In vitro, we demonstrate that normal mouse platelets, but not P-selectin-deficient platelets, bound to control tumor cells and protected them from leukocyte-mediated cytolysis. Conversely, treatment of tumor cells with disaccharide markedly reduced the ability of normal platelets to protect them from cytolysis. Finally, in an experimental metastasis model, we show that treatment of tumor cells with the disaccharide markedly reduced their lung colonization potential after injection into severe combined immunodeficient mice. These findings suggest that this compound may represent a novel class of chemotherapeutic agents for prevention and treatment of metastatic disease.

Adenocarcinoma↗
PubMed1992

Structural analysis of the linkage region oligosaccharides and unsaturated disaccharides from chondroitin sulfate using CarboPac PA1.

Swarm rat chondrosarcoma cell cultures were metabolically labeled with [35S]sulfate, [3H]glucose, or [3H]glucosamine. Chondroitin sulfate chains were isolated from purified aggrecan using alkaline borohydride treatment and Superose 6 chromatography. Various linkage region oligosaccharide alditols were derived from these chains using sequential chondroitinase digestions (ABC lyase followed by ACII lyase). They were then further processed by mercuric acetate treatment, which removed the 4,5-unsaturated uronosyl residue from the nonreducing end of the linkage, and then beta-galactosidase digestion which liberated the 2 galactose residues from the xylitol reducing terminus. Alkaline phosphatase digestions were performed to verify the presence of phosphate esters. All linkage region structures were isolated and identified using a combination of Progel-TSK G2500 and CarboPac PA1 chromatography steps in conjunction with monosaccharide analyses. This study revealed that chondroitin sulfate chains from aggrecan synthesized by rat chondrosarcoma cells in vitro have the following properties: 1) three out of every four of their linkage regions carry a phosphate ester on xylose, 2) nearly three out of every five chains begin the repeating disaccharide region with an unsulfated first disaccharide unit, 3) nearly twice as many nonphosphorylated chains have a sulfated first disaccharide than their phosphorylated counterparts, and 4) the vast majority of these chains do not contain sulfated galactose in their linkage regions. This report also describes a borohydride reduction procedure to confer alkali stability to the 3-substituted, unsaturated disaccharides derived from chondroitinase digests of chondroitin sulfate. Furthermore, a CarboPac PA1 method is demonstrated that separates these reduced disaccharides with exceptional resolution.

Animals↗
PubMed1984

The biosynthesis of gram-negative endotoxin. Formation of lipid A disaccharides from monosaccharide precursors in extracts of Escherichia coli.

We have discovered an enzyme in the cytosol of Escherichia coli that generates lipid A disaccharides from monosaccharide precursors by the following route: 2,3-diacyl-GlcN-1-P + UDP-2,3-diacyl-GlcN---- 2,3-diacyl-GlcN (beta, 1----6) 2,3-diacyl-GlcN-1-P + UDP. Previous studies from our laboratory have documented the presence in vivo of the precursors 2,3-diacylglucosamine 1-phosphate (2,3-diacyl-GlcN-1-P) (lipid X of E. coli) and UDP-2,3-diacylglucosamine (UDP-2,3-diacyl-GlcN) (Bulawa, C.E., and Raetz, C.R.H.J. Biol. Chem. 259, 4846-4851). Both substrates are novel glucosamine-derived phospholipids, acylated with beta-hydroxymyristoyl moieties, and they accumulate in E. coli mutants defective in the pgsB gene. Synthetic ADP-, GDP-, and CDP-2,3-diacylglucosamines are inefficient substrates compared to the naturally occurring UDP derivative. The free-acid form of the tetraacyldisaccharide 1-phosphate product (C68H129N2O20P) that is generated in vitro has Mr = 1325.74 as judged by fast atom bombardment mass spectrometry. Mild acid hydrolysis (0.1 M HCl for 30 min at 100 degrees C) liberates greater than 95% of the phosphate moiety as Pi. Detailed analysis by 1H and 13C NMR spectroscopy confirms the presence of a phosphate residue at position 1 of the disaccharide, an alpha-anomeric configuration at the reducing end, and a beta, 1----6 linkage between the two glucosamines. Importantly the disaccharide 1-phosphate synthase is missing in extracts of E. coli strains harboring the pgsB1 mutation, consistent with the massive accumulation of 2,3-diacyl-GlcN-1-P and UDP-2,3-diacyl-GlcN in vivo. The enzymatic reaction reported here represents a major biosynthetic route for the formation of lipid A disaccharides in E. coli and other Gram-negative bacteria. An in vitro system for the biosynthesis of lipid A disaccharides has not been described previously.

Disaccharides↗
PubMed1998

Water content and glycosaminoglycan disaccharide concentration of the canine meniscus.

OBJECTIVE: To determine the regional composition of water and glycosaminoglycan (GAG) disaccharides of the canine meniscus. SAMPLE POPULATION: 52 menisci from the stifle of dogs. PROCEDURE: Regional sections of each meniscus were weighed, dried, and reweighed to determine water content. Dried tissue specimens were subjected to enzymatic digestion. Analysis and quantification of disaccharide degradation products were performed, using high-performance liquid chromatography. RESULTS: Water content was approximately 65% in polar and central regions of the canine meniscus. Water content of the central region of the lateral meniscus was significantly higher than that of the medial meniscus (P = 0.0090). Chondroitinase digestion of canine meniscal tissue yielded detectable delta Di-HA, delta Di-4S, and delta Di-6S GAG disaccharides. Disaccharides specific to dermatan sulfate and chondroitin D or E sulfate were not detected. Concentrations of delta Di-4S and delta Di-6S were significantly greater in the lateral central region, compared with the medial central region (P = 0.0005 and 0.0002, respectively). CONCLUSION: Water content and delta Di-4S and delta Di-6S concentrations were significantly lower in the central region of the medial meniscus, compared with the central region of the lateral meniscus. Reduced tissue hydration of the medial central region may have been a direct result of its overall decrease in total GAG content. CLINICAL RELEVANCE: The ability to evaluate subtle differences in tissue GAG composition by analytical measurement of their constituent disaccharides may aid in the understanding of the complex material properties of the normal and diseased meniscus, which may be applied to the study of meniscal healing and biomechanics.

Animals↗
PubMed1997

Synthesis of alpha- and beta-D-(1-->6)-C-Disaccharides by Wittig Olefination of Formyl C-Glycosides with Glycopyranose 6-Phosphoranes.

The synthesis of (1-->6)-C-disaccharides by Wittig condensation of formyl C-glycofuranosides and pyranosides with galacto- and glucopyranose 6-phosphoranes is described herein. The method involves the coupling of the sugar aldehydes with the ylides and the reduction of the double bond of the resulting sugar alkenes, in most of the cases by catalytic hydrogenation. The reduction with nickel boride or diimide is employed in some special cases. O-Benzyl protective groups are removed by catalytic hydrogenation either in the course of the reduction of the double bond or in a subsequent step, while O-isopropylidene groups are cleaved by treatment with Amberlite IR-120. In this way, eight free beta-D-(1-->6)-C-disaccharides have been prepared in 26-61% overall yield starting from beta-linked formyl C-glycosides. These include C-linked analogues of the biologically active disaccharides allolactose (Galbeta1,6Glc), gentiobiose (Glcbeta1,6Glc), and N-acetylamino disaccharides (GalNHAcbeta1,6Gal and GalNHAcbeta1,6Glc). Moreover, the synthesis of two alpha-D-(1-->6)-C-disaccharides is described from formyl C-furanosides. The limiting condition of the synthesis of these stereoisomers is the configurational instability of the alpha-linked formyl C-glycosides under the basic conditions of the Wittig olefination.

Journal Article↗
PubMed2001

Keratan sulfate disaccharide composition determined by FACE analysis of keratanase II and endo-beta-galactosidase digestion products.

Many tissues contain glycoproteins and proteoglycans, which are substituted with N-or O-linked keratan sulfate, a glycosaminoglycan in which the lactosamine (-galbeta1,4glcNAc-) disaccharide backbone is variably modified by sulfation, fucosylation, and sialylation. We report here a rapid, sensitive, and quantitative procedure for obtaining a complete disaccharide compositional analyses for keratan sulfates after FACE separation of products generated by hydrolysis of the glycosaminoglycans with B. fragillis keratanase II and E. freundii endo-beta-galactosidase. Seven digestion end products are separable in a single electrophoretic step using Monosaccharide composition gels. These are: the unsulfated disaccharide, glcNAcbeta1,3gal, the fucosylated trisaccharide, galbeta1,2[fucalpha1,3]glcNAc6S, the mono- and disulfated disaccharides, galbeta1,4glcNAc6S or gal6Sbeta1,4glcNAc6S from the chain interior, and the sialylated mono- and disulfated trisaccharides neuAalpha2,3galbeta1,4glcNAc6S or neuAalpha2,3gal6Sbeta1,4glcNAc6S from the nonreducing terminus. FACE analyses also revealed the presence of a contaminant beta-galactosidase activity in keratanase II enzyme preparations which cleaves the disaccharide, galbeta1,4glcNAc6S to its constituent monosaccharides, gal and glcNAc6S. It was particularly prominent at enzyme concentrations > 2 mU per nmole substrate glcNH(2) or after prolonged digestion times (> 12 h), and was not inhibitable by thiogalactosides or N-acetyl-lactosamine. As these monosaccharide products would not be detectable using the commonly described analytical methods for KS hydrolase products, such as (1)H-NMR and HPLC analyses, our data illustrate that the FACE procedure represents an improved approach for accurate compositional microanalyses of corneal and skeletal keratan sulfates, especially applicable to experimentation involving small amounts (1-2 microg) of this glycosaminoglycan.

Acetylglucosaminidase↗
PubMed1987

Requirement of a properly acylated beta(1-6)-D-glucosamine disaccharide bisphosphate structure for efficient manifestation of full endotoxic and associated bioactivities of lipid A.

Several synthetic acylated glucosamine monophosphates, with structures corresponding to the nonreducing or reducing moiety of the lipid A of the Escherichia coli or Salmonella minnesota type, and a synthetic compound corresponding to a biosynthetic disaccharide lipid A precursor (designated Ia or IVA) were examined for their endotoxic and related bioactivities in comparison with those of the synthetic and bacterial parent molecules, i.e., acylated beta(1-6)-D-glucosamine disaccharide bisphosphates. Some of the test monosaccharide compounds were definitely active in most of the in vitro assays. Their activities, except for complement activation, however, were weaker than those of the reference compounds, synthetic and bacterial acylated disaccharide bisphosphates. The differences between the test monosaccharide and disaccharide compounds were much more apparent in in vivo assays, in which the test acylated glucosamine monophosphates were scarcely active, though some test compounds exhibited weak lethal toxicity in galactosamine-loaded mice and were weakly active in pyrogenicity, immunoadjuvant activity, and possible tumor necrosis factor and alpha and beta interferon-inducing ability in Mycobacterium bovis BCG- and Propionibacterium acnes-primed mice, respectively. Mixture at an equimolar ratio of acyl glucosamine monophosphates, each of which has the structure of the reducing or nonreducing moiety of the reference disaccharide compound, did not restore the endotoxic or associated bioactivities of the corresponding parent molecules. No essential differences in bioactivity were noted between synthetic and bacterial monosaccharide compounds, i.e., lipid X, whose structure corresponds to the reducing moiety of E. coli-type lipid A.

Acylation↗
PubMed2005

Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives.

BACKGROUND: Many polyhydroxylated piperidines are inhibitors of the oligosaccharide processing enzymes, glycosidases and glycosyltransferases. Aza-C-linked disaccharide mimetics are compounds in which saturated polyhydroxylated nitrogen and oxygen heterocycles are linked by an all-carbon tether. The saturated oxygen heterocycle has the potential to mimic the departing sugar in a glycosidase-catalysed reaction and aza-C-linked disaccharide mimetics may, therefore, be more potent inhibitors of these enzymes. RESULTS: The scope, limitations and diastereoselectivity of the dihydroxylation of stereoisomeric 2-butyl-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahydro-pyridin-3-ols is discussed. In the absence of a 6-substituent on the piperidine ring, the Upjohn (cat. OsO4, NMO, acetone-water) and Donohoe (OsO4, TMEDA, CH2Cl2) conditions allow complementary diastereoselective functionalisation of the alkene of the (2R*,3R*) diastereoisomer. However, in the presence of a 6-substituent, the reaction is largely controlled by steric effects with both reagents. The most synthetically useful protocols were exploited in the two-directional synthesis of aza-C-linked disaccharide analogues. A two-directional oxidative ring expansion was used to prepare bis-enones such as (2R,6S,2'S)-6-methoxy-2-(6-methoxy-3-oxo-3,6-dihydro-2H-pyran-2-ylmethyl)-1-(toluene-4-sulfonyl)-1,6-dihydro-2H-pyridin-3-one from the corresponding difuran. Selective substitution of its N,O acetal was possible. The stereochemical outcome of a two-directional Luche reduction step was different in the two heterocyclic rings, and depended on the conformation of the ring. Finally, two-directional diastereoselective dihydroxylation yielded seven different aza-C-linked disaccharide analogues. CONCLUSION: A two-directional approach may be exploited in the synthesis of aza-C-linked disaccharide mimetics. Unlike previous approaches to similar molecules, neither of the heterocyclic rings is directly derived from a sugar, allowing mimetics with unusual configurations to be prepared. The work demonstrates that highly unsymmetrical molecules may be prepared using a two directional approach. The deprotected compounds may have potential as inhibitors of oligosaccharide-processing enzymes and as tools in chemical genetic investigations.

Journal Article↗
PubMed2003

Laser-induced fluorescence as a powerful detection tool for capillary electrophoretic analysis of heparin/heparan sulfate disaccharides.

In quest for high sensitivities necessary for determining the disaccharide composition of heparin/heparan sulfate present in trace amounts in biologic samples, an ultrahighly sensitive capillary electrophoresis (CE) method using laser-induced fluorescence (LIF) detection was developed. Heparin/heparan sulfate-derived Delta-disaccharides were derivatized with the fluorophore 2-aminoacridone and resolved by a reversed-polarity CE method. Estimation of the limit of detection in concentration term and limit of quantitation showed that LIF detection of AMAC-derivatives of Delta-disaccharides resulted in 27-744 times higher sensitivity as compared to those detected by UV at 255 nm. These data suggest that CE-LIF is a powerful tool to quantify minute amounts of heparin/heparan sulfate disaccharides.

Disaccharides↗
PubMed1985

Use of chemical ionization in gas chromatographic/mass spectrometric screening of human urine for disaccharides containing inositol.

Gas chromatography/mass spectrometry (GC/MS) in the positive chemical ionization (CI) mode was used to screen normal urine for inositol-containing disaccharides in the form of permethylated derivatives, after borodeuteride reduction of the reducing saccharides. Ammonia was the reactant gas. The results revealed the existence of deoxyhexosyl-inositol and hexosyl-inositol disaccharides, and of a new compound, N-acetylhexosaminyl-inositol disaccharide. Up to four isomers of deoxyhexosyl-inositol could be present in the same sample even though only one of them has so far been fully characterized in man. As regards the hexosyl-inositols, one to three isomers were present in the same sample and probably corresponded to the three isomers of galactosyl-inositol recently described in man. N-Acetylhexosaminyl-inositol (identified elsewhere by us as N-acetylgalactosaminyl-alpha (1-1)-myo-inositol) was seen in only a few samples. No relationship can be found between the excretion of all these inositol-containing disaccharides on the one hand, ABO(H) blood group and 'Secretor' status (Se or sese) of the donors on the other. The gas chromatographic CI mass spectrometric technique used here with various ammonia pressures can be applied to the screening of other biological fluids or tissues for inositol glycosides.

Disaccharides↗
PubMed1996

High performance capillary electrophoresis method to characterize heparin and heparan sulfate disaccharides.

A rapid, sensitive and accurate high-performance capillary electrophoresis method is described for the determination of the sulfation pattern of heparin and heparan sulfate disaccharides. The analysis, performed after enzymic degradation of the polysaccharides with heparinase and heparinases II and III in combination, yields highly UV-absorbing delta-disaccharides. The separation is performed with reversed polarity using 15 mM phosphate buffer, pH 3.50. This method is superior to others since all known 12 disaccharides carrying N-acetylated, N-sulfated or unsubstituent glucosamine can be separated in a single run of 15 min. At the highest sensitivity the analysis consumes only a few femtograms of glycosaminoglycan and allows a determination of delta-disaccharides at the attomole level.

Carbohydrate Sequence↗