Oligosaccharide Glycosides Research Articles

A highly lipophilic sulfated tetrasaccharide glycoside related to muparfostat (PI-88) exhibits virucidal activity against herpes simplex virus

Although sulfated polysaccharides potently inhibit the infectivity of herpes simplex virus (HSV) and human immunodeficiency virus in cultured cells, these compounds fail to show protective effects in humans, most likely due to their poor virucidal activity. Herein we report on sulfated oligosaccharide glycosides related to muparfostat (formerly known as PI-88) and their assessment for anti-HSV activity. Chemical modifications based on the introduction of specific hydrophobic groups at the reducing end of a sulfated oligosaccharide chain enhanced the compound's capability to inhibit the infection of cells by HSV-1 and HSV-2 and abrogated the cell-to-cell transmission of HSV-2. Furthermore, modification with a highly lipophilic cholestanyl group provided a compound with virucidal activity against HSV. This glycoside targeted the viral particle and, to a lesser degree, the cell, and exhibited an antiviral mode of action typical for sulfated polysaccharides and virucides, i.e., interference with the virus attachment to cells and irreversible inactivation of virus infectivity, respectively. The virucidal activity was decreased in the presence of human cervical secretions suggesting that higher doses of this glycoside might be needed for in vivo application. Altogether, the sulfated oligosaccharide-cholestanyl glycoside exhibits potent anti-HSV activity and is, therefore, a good candidate for development as a virucide.

Synthesis and Biological Evaluation of Polysulfated Oligosaccharide Glycosides as Inhibitors of Angiogenesis and Tumor Growth

A series of polysulfated penta- and tetrasaccharide glycosides containing alpha(1-->3)/alpha(1-->2)-linked mannose residues were synthesized as heparan sulfate (HS) mimetics and evaluated for their ability to inhibit angiogenesis. The compounds bound tightly to angiogenic growth factors (FGF-1, FGF-2, and VEGF) and strongly inhibited heparanase activity. In addition, the compounds exhibited potent activity in cell-based and ex vivo assays indicative of angiogenesis, with tetrasaccharides exhibiting activity comparable to that of pentasaccharides. Selected compounds also showed good antitumor activity in vivo in a mouse melanoma (solid tumor) model resistant to the phase III HS mimetic 1 (muparfostat, formerly known as PI-88). The lipophilic modifications also resulted in reduced anticoagulant activity, a common side effect of HS mimetics, and conferred a reasonable pharmacokinetic profile in the rat, as exemplified by the sulfated octyl tetrasaccharide 5. The data support the further investigation of this class of compounds as potential antiangiogenic, anticancer therapeutics.

Conceivably the first example of a phase transition in aqueous solutions of oligosaccharide glycosides. Evidence from variable-temperature 1H NMR and optical rotation measurements for a solution of allyl lactoside

Conceivably the first example of a phase transition in aqueous solutions of oligosaccharide glycosides. Evidence from variable-temperature 1H NMR and optical rotation measurements for a solution of allyl lactoside

Synthesis of sulfated oligosaccharide glycosides having high anti-HIV activity and the relationship between activity and chemical structure

Sulfated laminara-oligosaccharide glycosides having high anti-human immunodeficiency virus (HIV) activities were synthesized from laminara-tetraose, -pentaose and -hexaose. The oligosaccharide glycosides were synthesized by treating peracetylated β-oligosaccharides with various alcohols and Lewis acid catalysts. The effects of the number of glucose residues and the alkyl chain-length on anti-HIV activity were examined. The anti-HIV activity of sulfated dodecyl laminara-pentaosides and -hexaosides increased with increasing degree of sulfation (DS) and the pentaoside having an almost fully-sulfated saccharide portion had the highest activity, whereas for the hexaoside a somewhat lower DS manifested the highest activity. Sulfated laminara-oligosaccharide glycosides having fluoroalkyl-containing aglycons of high hydrophobicity showed potent inhibitory effects against HIV infection. In contrast, hydrophilic substituents containing oligo(ethyleneoxy) groups as aglycons in the sulfated oligosaccharides did not show high anti-HIV activity.

Syntheses of 2-deoxy-2-fluoro mono- and oligo-saccharide glycosides from glycals and evaluation as glycosidase inhibitors

Several fluorinated oligosaccharides, including 2-deoxy-2-fluoro derivatives of cellobiose, maltose, and maltotriose were synthesized by the action of fluorine or acetyl hypofluorite on the corresponding glycal peracetates. Temperature effects on the stereoselectivities of these reactions were examined. Addition of acetyl hypofluorite to several 2-substituted glycals in the gluco or galacto series gave 2,2-disubstituted arabino- or lyxo-hexose derivatives; 3,4,6-tri- O-acetyl-2-fluoro- d-glucal or the analogous galactal yielded 2-deoxy-2,2-difluoro arabino- or lyxo-hexose peracetates, whereas 2-acetoxy-3,4,6-tri- O-acetyl- d-glucal or the analogous galactal gave 2( R)-2-acetoxy-2-fluoro- arabino- or lyxo-hexose peracetates, respectively. 2-Acetamido-3,4,6-tri- O-acetyl- d-glucal gave 2( R)-2-acetamido-2-acetoxy-3,4,6-tri- O-acetylα- d- arabino-hexopyranosyl fluoride. 2,4-Dinitrophenyl 2-deoxy-2-fluoro-β-cellobioside was an inactivator of the exoglucanase from Cellulomonas fimi while 2-deoxy-2-fluoro-α-maltosyl and α-maltotriosyl fluorides were slow substrates of human pancreatic alpha-amylase and rabbit muscle glycogen debranching enzyme, respectively.

Stereoselective syntheses of a di-, tri-, and tetra-saccharide fragment of shigella dysenteriae type 1 O-antigen using 3,4,6-tri- O-acetyl-2-azido-2-deoxy-α- d-glucopyranosyl chloride as a glycosyl donor

Methyl 2,4-di- O-benzoyl-α- l-rhammopyranoside ( 1) furnished a crystalline 3- O-bromoacetyl derivative that was treated with the dichloromethyl methyl ether-ZnCl 2 reagent to give 2,4-di- O-benzoyl-3- O-bromoacetyl-α- l-rhamnopyranosyl chloride ( 3). Compounds 1 and 3 were condensed under the conditions of base-deficient, silver trifluoromethanesulfonate-mediated glycosylation to give a fully protected rhamnobioside, which on O-debromoacetylation afforded the disaccharide nucleophile 10. Similar condensation of 3 with methyl 3- O-benzoyl-4,6- O-benzylidene-α- d-galactopyranoside, followed by O-debromoacetylation and condensation of the thus formed methyl O-(2,4-di- O-benzoyl-α- l-rhamnopyranosyl)-(1 → 2)-4,6- O-benzylidene-3- O-benzoyl-α- d-galactopyranoside again with 3, gave the trisaccharide glycoside. Subsequent O-debromoacetylation gave 17, having only HO-3 3 unsubstituted. Silver perchlorate-mediated glycosylations of 1, 10, and 17 with 3,4,6-tri- O-acetyl-2-azido-2-deoxy-α- d-glucopyranosyl chloride afforded, with high α stereoselectivity, protected di-, tri-, and tetra-saccharide glycosides. Subsequent hydrogenation, followed by N-acetylation and O-deacylation, afforded three oligosaccharide glycosides having nonreducing terminal 2-acetamido-2-deoxy-α- d-glucopyranosyl residues and comprising successively larger portions of the repeating unit of Shigella dysenteriae type 1 O-antigen.

Binding studies on internal immunodeterminants: synthesis of β-(1 → 6)-linked oligosaccharide methyl glycosides having one to four internal d-galactopyranosyl residues flanked by gentiobiose residues

The oligosaccharide glycosides β- d-Glc p-(1 → 6)-β- d-Glc p-(1 → 6)-[β- d-Gal p-(1 → 6)] n -β- d-Glc p-(1 → 6)-β- d-Glc p-1 → OMe ( n = 1−4) were prepared by a convergent block synthesis. Haloacetyl, tert-butyldiphenylsilyl, and dimethylthexylsilyl groups were used as temporary protective groups for the preparation of the intermediate glycosyl donors and acceptors. The deoxygenated trisaccharide glycosides β- d-Glc p-(1 → 6)-β- d-Gal p-(1 → 6)-4-deoxy-β- d- xylo-Hex p-1 → OMe and β- d-Glc p-(1 → 6)-4-deoxy-β- d- xylo-Hex p-(1 → 6)-β- d-Gal p-1 → OMe were also synthesized. The binding of each glycoside to the monoclonal antigalactan antibody IgA J539 was studied and the results support the previous finding that J539 can bind to internal antigenic epitopes. The data are consistent with the interpretation that subsite C of that antibody binds glucose with a K a of ∼ 6 (cf. 10.9 for galactose).

α-Mannosidase-catalysed synthesis of novel manno-, lyxo-, and heteromanno-oligosaccharides: A comparison of kinetically and thermodynamically mediated approaches

The α-mannosidase from jack bean has been used to catalyse the production of a range of novel oligosaccharides and oligosaccharide derivatives. p-Nitrophenyl oligosaccharide glycosides have been synthesized by glycosyl transfer from p-nitrophenyl α-mannoside donor to a range of p-nitrophenyl glycoside acceptors. Oligosaccharides have also been synthesized by the condensation of mannose with a range of mono- and oligosaccharide acceptors. The structures of oligosaccharides formed from mannose by condensation have been investigated by methylation analysis and NMR spectroscopy.

Influence of Various Parameters on the Yield and Regioselectivity of Glycosidase‐catalyzed Formation of Oligosaccharide Glycosides

Annals of the New York Academy of SciencesVolume 542, Issue 1 p. 383-389 Influence of Various Parameters on the Yield and Regioselectivity of Glycosidase-catalyzed Formation of Oligosaccharide Glycosides KURT G. I. NILSSON, KURT G. I. NILSSON Swedish Sugar Company, Limited S-232 00 Arlöv, SwedenSearch for more papers by this author KURT G. I. NILSSON, KURT G. I. NILSSON Swedish Sugar Company, Limited S-232 00 Arlöv, SwedenSearch for more papers by this author First published: December 1988 https://doi.org/10.1111/j.1749-6632.1988.tb25861.xCitations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume542, Issue1Enzyme Engineering 9December 1988Pages 383-389 RelatedInformation

Artificial carbohydrate antigens: the synthesis of the tetrasaccharide repeating unit of Shigella flexneri O antigen

The synthesis of a tetrasaccharide glycoside, 8-methoxycarbonyloctyl O-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1 → 2)-O-α-L-rhamnopyranosyl-(1 → 2)-O-α-L-rhamnopyranosyl-(1 → 3)-α-L-rhamnopyranoside, representing the repeating unit of the Shigella flexneri serogroup Y O antigen is reported, together with that of a component trisaccharide. Both oligosaccharide glycosides are functionalised to permit covalent attachment to immunogenic carriers and solid matrices. A key intermediate used to establish α-1,2-rhamnopyranoside linkages was 2-O-acetyl-3,4-di-O-benzyl-α-L-rhamnopyranosyl chloride (1), which was obtained in quantitative yield from 3,4-di-O-benzyl-1,2-O-(methoxyethylidene)-β-L-rhamnopyranose. Thus 8-methoxycarbonyloctyl 3,4-di-O-benzyl-α-L-rhamnopyranoside (2) prepared from the rhamnopyranosyl chloride 1 was used in a second Koenigs–Knorr reaction to provide an α-1,2-linked disaccharide. The disaccharide is in turn glycosylated at the C-2′ position with tri-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranosyl bromide to provide the trisaccharide glycoside, 8-methoxycarbonyloctyl O-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1 → 2)-O-α-L-rhamnopyranosyl-(1 → 2)-α-L-rhamnopyranoside. Application of the same reaction sequence to a rhamnopyranoside selectively blocked with benzoate esters at C-2 and C-4 gave the S. flexneri tetrasaccharide repeating unit. The success of this strategy was dependent upon the ability to use selective transesterification conditions, which permit removal of O acetate groups whilst leaving benzoate esters intact.

Studies of the structures of the carbohydrate components in plant oligosaccharide glycosides by the dithioacetal method

The usefulness of the dithioacetal method for studies of carbohydrate structures has been demonstrated by analyzing the constituent monosaccharides and aldehydes in the products of periodate oxidation of a number of oligosaccharide glycosides from plants.

Mass spectrum studies of natural products; cardenolides

AbstractThe mass spectrometry of cardenolides is briefly reviewed. Recent developments in the characterization of the cardiac glycosides by a combination of electron impact and field ionization methods are discussed, with emphasis on the information obtained regarding the sequence of monosaccharide residues in the case of oligosaccharide glycosides. Recent efforts to understand the detailed fragmentation behaviour of cardenolide aglycones in terms of their structure and substitution pattern are also discussed.

Cleavage of oligosaccharide glycosides by means of dihalomethyl methyl ethers: a novel preparation of rutinose

Cleavage of oligosaccharide glycosides by means of dihalomethyl methyl ethers: a novel preparation of rutinose