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M Kiso

Publications and source records attributed to M Kiso.

At least 127 records · Page 7Linked to original sources
PubMed1992

Synthesis of the methyl thioglycosides of deoxy-N-acetyl-neuraminic acids for use as glycosyl donors.

Methyl 2-thioglycoside derivatives of 4-, 7-, 8-, and 9-deoxy-N-acetylneuraminic acids have been prepared as glycosyl donors for the synthesis of sialoglycoconjates. Reduction of a (phenoxy)thiocarbonyl group, selectively introduced at the 4 position of methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-8,9-O-isopropylidene-D- glycero-alpha-D-galacto-2-nonulopyranosid]onate (1), gave the 4-deoxy compound, which was transformed via O-deisopropylidenation, acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, subsequent acetylation, and displacement of the 2-acetoxy group by a methylthio group, into methyl (methyl 5-acetamido-7,8,9-tri-O-acetyl-3,4,5-trideoxy-2-thio-D-manno-2- nonulopyranosid)onate (17). Methyl [2-(trimethylsilyl)ethyl 5-acetamido-8,9-di-O-acetyl-4-O-benzoyl- 3,5,7-trideoxy-alpha-D-galacto-2-nonulopyranosid]onate, prepared from 1 in five steps, and methyl [2-(trimethylsilyl)ethyl 5-acetamido-4,7,9-tri-O-acetyl-3,5,8-trideoxy-alpha-D-galacto-2- nonulopyranosid]onate, prepared from 1 in six steps, were converted via selective removal of the 2-(trimethylsilyl)ethyl group, O-acetylation, and displacement of the 2-acetoxy group by a methylthio group as described for 17, into the corresponding methyl 7- and 8-deoxy-2-thioglycosides. Reductive dechlorination of methyl [2-(trimethylsilyl)ethyl 5-acetamido-4,7-di-O-benzoyl-9-chloro-3,5,9-trideoxy-D-glycero-alpha-D-g alacto- 2-nonulopyranosid]onate, prepared from methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosid++ +]onate by selective 9-O-tert-butyldimethylsilylation, benzoylation, removal of the 9-silyl group, and selective chlorination, gave a 9-deoxy compound. This was transformed, via O-debenzoylation, O-acetylation, selective removal of the 2(trimethylsilyl)ethyl group, 2-O-acetylation, 2-chlorination, displacement with potassium thioacetate, selective S-deacetylation, and S-methylation, into the methyl 2-thio-alpha-glycoside of 9-deoxy-N-acetylneuraminic acid.

Carbohydrate Conformation↗
PubMed1992

Synthesis of a series of ganglioside GM3 analogs containing a deoxy-N-acetylneuraminic acid residue.

Ganglioside GM3 analogs containing 4-, 7-, 8-, and 9-deoxy-N-acetylneuraminic acids in the place of N-acetylneuraminic acid (Neu5Ac) have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-beta-D-galactopyranosyl)-(1----4)-2,6-di- O-benzoyl-beta-D-glucopyranoside with the methyl 2-thioglycoside derivatives of the respective deoxy-N-acetylneuraminic acids, using dimethyl(methylthio)sulfonium triflate as a promoter, gave the four required 2-(trimethylsilyl)ethyl alpha-sialosyl-(2----3b)-beta-lactosides. These were converted via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the corresponding alpha-sialosyl-(2----3b)-alpha-lactose trichloroacetimidates 15, 17, 19, and 21. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 15, 17, 19, and 21 in the presence of boron trifluoride etherate afforded the expected beta glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and de-esterification, into the target compounds.

Carbohydrate Conformation↗
PubMed1992

Synthesis of an S-(alpha-sialosyl)-(2----9)-O-(alpha-sialosyl)-(2----3')-beta-lactos ylceramide.

A ganglioside GD3 analog has been synthesized having an N-acetylneuraminic acid (Neu5Ac) residue alpha-thioglycosidically linked to C-9 of the Neu5Ac residue in the ganglioside GM3 structure. Glycosylation of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-beta-D-galactopyranosyl)-(1----4)-2,6-di-O-benzoyl-beta-D -glucopyranoside with methyl (methyl 5-acetamido-4,7,8-tri-O-acetyl-9-bromo-3,5,9-trideoxy-D-glycero-alpha-D- galacto-2-nonulopyranosid)onate, which was prepared from methyl (methyl 5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2- nonulopyranosid)onate by 8,9-O-isopropylidenation, O-acetylation, hydrolysis of the isopropylidene group, selective bromination, and O-acetylation, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the alpha-sialosyl-(2----3')-lactoside 8. Coupling of the O-acetyl derivative of 8 with the sodium salt of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-alpha-D- galacto-2-nonulopyranosonate gave an alpha-thioglycosidically linked tetrasaccharide. This was converted, via selective removal of the 2-(trimethylsilyl)ethyl group, trichloroacetimidation, and glycosidation with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol into a ganglioside precursor. Finally the precursor on selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and de-esterification gave the analog, S-(N-acetyl-alpha-neuraminosyl)-(2----9)-O-(N-acetyl-9-thio-alpha- neuraminosyl)-(2----3')-beta-lactosylceramide.

Antigens, CD↗
PubMed1992

Synthesis of a position isomer of ganglioside GD3 having an alpha-Neu5Ac-(2----9)-alpha-Neu5Ac linkage.

A position isomer of ganglioside GD3 has been synthesized in which N-acetylneuraminic acid (Neu5Ac) is linked alpha-glycosidically at C-9 of the Neu5Ac residue of the ganglioside GM3, structure. The coupling of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-beta-D-galactopyranosyl)-(1----4)-2,6-di-O-benzoyl-beta-D -glucopyranoside with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2-nonulopyranosylonate)-(2----9)-(methyl 5-acetamido-4,7,8-tri-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2 -nonulopyranosid)onate, prepared from the corresponding 2-(trimethylsilyl)ethyl glycoside by selective removal of the 2-(trimethylsilyl)ethyl group, 1-O-acetylation, and introduction of the methylthio group with trimethyl(methylthio)silane, using N-iodosuccinimide-trifluoromethanesulfonic acid as a glycosylation catalyst, gave a tetrasaccharide (5). Compound 5 was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into a protected alpha-Neu5Ac-(2----9)-alpha-Neu5Ac-(2----3')-alpha-lactosyl trichloroacetimidate (8). Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 8 afforded a ceramide precursor which was transformed, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester groups, into to the little ganglioside.

Carbohydrate Sequence↗
PubMed1992

Immunosuppression induced by non-reducing acylated monosaccharide subunits of lipid A.

Synthetic acylated glucosamine monosaccharides, representative of the non-reducing subunit of lipid A, were compared for their ability to induce non-specific suppression of antibody forming cells. Five of nine analogs were found to be functional in this respect, indicating that these compounds, carrying a phosphate at C4 and acyl substituents at C2 and C3 are the smallest synthetic analogs of lipid A capable of eliciting non-specific immunosuppression. A comparison of the analogs inducing suppression with those testing negative revealed that (i) a single 3-hydroxymyristoyl group at C2 is common to 4/5 analogs inducing suppression; (ii) addition of an oxytetradecanoyl group to the 3-hyroxymyristoyl group at either C2 or C3 negated suppression; and (iii) extreme specificity was exhibited in suppression induction such that substitution of either lauric (C12) or palmitic (C16) for myristic acid (C14) at C2 voided transmission of the suppressive signal.

Animals↗
PubMed1992

The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide.

The selectins (lectin-EGF-complement binding-cell adhesion molecules [LEC-CAMs]) are a family of mammalian receptors implicated in the initial interactions between leukocytes and vascular endothelia, leading to lymphocyte homing, platelet binding, and neutrophil extravasation. The three known selectins, L-selectin (leukocyte adhesion molecule-1 [LECAM-1]), E-selectin (endothelial-leukocyte adhesion molecule-1 [ELAM-1]), and P-selectin (GMP-140) share structural features that include a calcium-dependent lectin domain. The sialyl Lewis(x) carbohydrate epitope has been reported as a ligand for both E- and P-selectins. Although L-selectin has been demonstrated to bind to carbohydrates, structural features of potential mammalian carbohydrate ligand(s) have not been well defined. Using an ELISA developed with a sialyl Lewis(x)-containing glycolipid and an E-selectin-IgG chimera, we have demonstrated the direct binding of the L-selectin-IgG chimera to sialyl Lewis(x). This recognition was calcium dependent, and could be blocked by Mel-14 antibody but not by other antibodies. Recognition was confirmed by the ability of cells expressing the native L-selectin to adhere to immobilized sialyl Lewis(x). These data suggest that the sialyl Lewis(x) oligosaccharide may form the basis of a recognition domain common to all three selectins.

Animals↗
PubMed1992

Substrate specificity of the Trypanosoma cruzi trans-sialidase.

Trypanosoma cruzi trypomastigotes acquire sialic acid (SA) from host glycoconjugates by means of a plasma membrane-associated trans-sialidase (TS). Here we study the substrate specificity of TS, which differs from all known sialyltransferases in that it does not require cytidine monophosphate (CMP)-SA as donor. The T. cruzi TS reversibly transfers SA to saccharides with terminal beta-Gal (but not alpha-Gal) residues. Donors are saccharides with SA linked to terminal beta-Gal residues by (alpha 2-3), but not (alpha 2-6) bonds. The type of beta-linkage of the terminal Gal residue is of minor importance (beta 1-4 and beta 1-6 are slightly better than beta 1-3), whereas chain length and the structure of additional vicinal sugar residues are not relevant. SA on the surface of living trypomastigotes of T. cruzi is transferred back and forth between the parasite surface and acceptor molecules with terminal beta-Gal, either in solution or on the surface of neighbouring mammalian cells. Addition of fucose residue on or close to the terminal galactose impairs TS activity. As a consequence, the enzyme acts poorly on the E-selectin ligand sialyl-Lewisx and its precursor Lewisx, and in vitro adhesion of TS-treated neutrophils to L-cells expressing L-selectin is not affected. Modifications in the structure of the (alpha 2-3)-linked N-acetyl-neuraminic acid (Neu5Ac) (deoxy or methoxy) of the donor molecules do not impair transfer if the changes are at C9, whereas changes at C4, C7 and C8 impair the ability to donate the modified SA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Modification of immunopharmacological activities of synthetic monosaccharide lipid A analogue, GLA60, by lysozyme.

Recent studies by our group suggested that lysozyme has a high affinity for bacterial lipopolysaccharide (LPS) of both the smooth and rough forms, and inhibits various immunomodulatory activities of LPS. GLA60 is a synthetic monosaccharide analogue of bacterial lipid A well known as having most of the activities of lipid A with very low toxicity. In this study, we characterized the interaction of lysozyme with GLA60 in comparison to that with Escherichia coli 0111 LPS (smooth form) by means of an immunopharmacological approach. Using dansylated lysozyme (DNS-LZM) as a probe, LZM was found to bind to GLA60. The mitogenic and polyclonal B-cell activating activities were significantly reduced by complex formation. However, there was no inhibitory effect on GLA60 induced production of IL-1 and TNF of macrophages. Interestingly, the activities of macrophages induced by the complex were found to be significantly higher than those induced by GLA60 itself. In contrast, the activities of 0111 LPS were significantly inhibited by LZM. Since the GLA60-LZM complex produced a turbid suspension but the 0111 LPS-LZM complex remained soluble, we consider that the activities of GLA60 alone were mediated by the common functional LPS receptor for dispersed form in both macrophages and B-lymphocytes, but activation of macrophages by the complex was mediated either by another LPS receptor not present in B-lymphocytes or through the phagocytic function of macrophages.

Adjuvants, Immunologic↗
PubMed1992

DT-5461, a new synthetic lipid A analogue, inhibits lung and liver metastasis of tumor in mice.

We have investigated the antimetastatic effect of a new synthetic lipid A analogue, of low endotoxicity, DT-5461, against two highly metastatic tumor cell lines, L5178Y-ML25 T-lymphoma and B16-BL6 melanoma cells in mice. Four intermittent i.v. administrations of DT-5461 at intervals of 4 days resulted in a significant inhibition of liver metastasis caused by i.v. injection of L5178Y-ML25 cells and lung metastasis of B16-BL6 cells in the experimental metastasis models. Intraperitoneal and intranasal administrations as well as i.v. administration of DT-5461 were also effective in preventing lung metastasis of the melanoma cells. Multiple administrations of DT-5461 before the surgical excision of primary tumors significantly reduced the number of lung colonies of melanoma cells and primary tumor size. Similarly, this treatment modality after the surgical excision of primary tumors showed a greater reduction of lung tumor colonies as compared with lipopolysaccharide, a synthetic lipid A (No. 506) and its analogue as well as untreated control in the spontaneous lung metastasis model. Furthermore, the group that received DT-5461 after the inoculation of lymphoma or melanoma cells showed significantly enhanced survival rate compared with the untreated control. These results suggested that DT-5461 may be therapeutically useful for the inhibition of tumor metastasis.

Animals↗
PubMed1991

Structural requirements for the carbohydrate ligand of E-selectin.

The acute inflammatory response requires that circulating leukocytes adhere to, and then migrate through, the vascular wall at the site of injury or infection. Several receptors have been implicated in this adhesion and migration process, including the selectins, a family of carbohydrate-binding proteins. The ligand for one of these proteins, E-selectin (LECAM-2, ELAM-1) has been described by several groups to contain a polylactosamine structure bearing a terminal sialic acid residue and at least one fucose residue. We report here a more detailed investigation into the minimum structural requirements for carbohydrate recognition by E-selectin. Using both direct binding and inhibition studies we demonstrate that the sialyl Lewisx tetrasaccharides Sia(alpha 2-3)Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc, and Sia(alpha 2-3)Gal(beta 1-4)[Fuc(alpha 1-3)]Glc are the smallest oligosaccharides recognized by the lectin. In addition, an oligosaccharide containing the sialyl Lewisa epitope is also recognized, but less avidly. We propose a structural model of functional groups necessary for recognition by E-selectin, based on these data and additional experiments on modifications of sialic acid and the reducing terminal saccharide.

Animals↗
PubMed1991

Regio- and stereo-selective synthesis of ganglioside GM1b and some positional analogs.

Total syntheses of ganglioside GM1b (IV3NeuAcGgOse4Cer) and three of its positional analogs are described. Methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D- glycero-alpha-D-galacto-2-nonulopyranosylonate)- (2----3)-2,4,6-tri-O-benzoyl-1-thio-beta-D-galactopyranoside (7) and methyl O-(methyl 5- acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2 -nonulopyranosylonate)-(2----6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio - beta-D-galactopyranoside (8) were the key glycosyl donors, prepared according to our reported methods. Coupling of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-alpha-D-galactopyranosyl bromide and 2-(trimethylsilyl)ethyl O-(2,3,6-tri-O-benzyl-beta-D- galactopyranosyl)-(1----4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside gave a trisaccharide, which after removal of O-acetyl and phthaloyl groups was converted separately, by benzylidenation and dibutyltin oxide-mediated selective benzylation, into two glycosyl acceptors. These were suitable respectively for C-3 and C-6 glycosylation reactions, promoted by dimethyl(methylthio)sulfonium triflate (DMTST), with the donors 7 and 8. The four possible coupling reactions gave the corresponding four pentasaccharide derivatives in high yields, and these were transformed into their respective alpha-trichloroacetimidates. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with the alpha-trichloroacetimidates gave the corresponding beta-glycosides, which on channeling through selective reduction of the azido group, coupling of the thus formed amino group with octadecanoic acid, O-deacetylation, and saponification of the methyl ester group, gave the title compounds.

Carbohydrate Sequence↗
PubMed1991

Synthesis of cerebroside, lactosyl ceramide, and ganglioside GM3 analogs containing beta-thioglycosidically linked ceramide.

Coupling of the sodium salt of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose, -beta-D-galactopyranose, O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1----4)-2,3,6-tri-O- acetyl- 1-thio-beta-D-glucopyranose, or O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2- nonulopyranosylonate)-(2----3)-O-(2,3-di-O-acetyl-6-O-bezoyl -beta-D- galactopyranosyl)-(1----4)-3-O-acetyl-2,6-di-O-benzoyl-1-thio-beta-D- glucopyranose, which were prepared from the corresponding 1-S-acetates, 1, 3, 6, and 9, with (2S,3R,4E)-2-azido-3-O-benzoyl-1-O-(p-tolylsulfonyl)-4-oc tadecene-1,3-diol (12) derived by tosylation of 11, gave the corresponding beta-thioglycosides 13, 17, 21, and 25, respectively in good yield. The beta-thioglycosides obtained were converted, via selective reduction of the azide group, condensation with octadecanoic acid, and removal of the protecting groups, into the title compounds.

Carbohydrate Sequence↗