Search results for "Tetrasaccharide"
showing 10 items of 12 documents
Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoG…
2019
This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths…
Spacer-separated sialyl LewisX cyclopeptide conjugates as potential E-selectin ligands.
2006
Completely protected sialyl LewisX azide was synthesized from a neolactosamine azide precursor carrying a 3-O-allyloxycarbonyl group as the temporary protecting group. After its Pd(0)-catalyzed deprotection and stereoselective alpha-fucosylation, the obtained LewisX azide was subjected to O-deacetylation in the galactose unit and subsequent regio- and stereoselective sialylation. Reduction of the anomeric azido group afforded the sialyl LewisX amine building block. Two molecules of this tetrasaccharide ligand were conjugated to a preformed cyclooctapeptide containing two equidistant l-asparagine units equipped with carboxy-terminated tetraethyleneglycol side chains to give, after deprotecti…
Junceosides A-C, new triterpene saponins from Arenaria juncea.
2002
Three novel triterpenoid saponins, junceosides A (1), B (2), and C (3), together with two known saponins have been isolated from the roots of Arenaria juncea. Their structures were elucidated using a combination of homo- and heteronuclear 2D NMR techniques (COSY, TOCSY, NOESY, HSQC, and HMBC) and by FABMS. The new compounds were characterized as 3-O-alpha-L-arabinopyranosyl-(1-->2)-[beta-D-galactopyranosyl-(1-->3)]-beta-D-glucuronopyranosylgypsogenin-28-O-beta-D-glucopyranosyl(1-->3)-[beta-D-xylopyranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-fucopyranoside (1), 3-O-alpha-L-arabinopyranosyl-(1-->2)-[beta-D-galactopyranosyl-(1-->3)]-beta-D-glucuronopyranosylgypsogenin-28-O-beta-D-x…
Characterisation of disaccharide fragments from the enzymatic digestion of heparin by liquid secondary ion mass spectrometry
1988
Disaccharide fragments resulting from the enzymatic digestion of heparins with heparinase have been purified by gel filtration chromatography and directly analyzed by positive and negative ion liquid secondary ion mass spectrometry (LSIMS). Following the chromatographic purification from excess sodium salt, the mass spectra of di- and tetrasaccharide fragment mixtures enabled the identification of up to three covalently bound sulfate moieties per glycosaminoglycan-disaccharide unit, by means of their molecular ions, containing the corresponding alkali-counterions.
Two New Glycosides from Astragalus caprinus
2001
A new glycoside of flavonol (1) and a new glycoside of a cycloartane-type triterpene (2) were isolated from the leaves and the roots of Astragalus caprinus, respectively. Their structures were elucidated in turn by spectroscopic data interpretation as 3-O-[[beta-D-xylopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->6)][beta-D-apiofuranosyl(1-->2)]]-beta-D-galactopyranosyl kaempferol (1) and 3-O-(beta-D-xylopyranosyl)-24-O-(beta-D-glucopyranosyl)-20,25-epoxycycloartane-3beta,6alpha,16beta,24alpha-tetrol (2).
A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors.
2006
An early step of the inflammatory response, the rolling of leukocytes on activated endothelial cells, is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialy Lewisx is a ligand for E-, P-, and L-selectin and therefore serves as a lead structure for the development of analogues. A combination of synthesis and structure-based design allowed rapid optimization. The current lead 2a was evaluated in our E-selectin cell flow chamber assay where it proved to inhibit rolling and adhesion with an IC50 of 28+/-7 microM. The assays used are predictive for the in vivo efficacy of test compounds as shown for 2a in a proteose peptone induced peritonitis model of acute inflammation in…
Polymeric Selectin Ligands Mimicking Complex Carbohydrates: From Selectin Binders to Modifiers of Macrophage Migration
2016
Novel polymeric cell adhesion inhibitors were developed in which the selectin tetrasaccharide sialyl-LewisX (SLeX ) is multivalently presented on a biocompatible poly(2-hydroxypropyl)methacrylamide (PHPMA) backbone either alone (P1) or in combination with O-sulfated tyramine side chains (P2). For comparison, corresponding polymeric glycomimetics were prepared in which the crucial "single carbohydrate" substructures fucose, galactose, and sialic acid side chains were randomly linked to the PHPMA backbone (P3 or P4 (O-sulfated tyramine)). All polymers have an identical degree of polymerization, as they are derived from the same precursor polymer. Binding assays to selectins, to activated endo…
Chemoenzymatic Synthesis of Functional Sialyl LewisX Mimetics with a Heteroaromatic Core
2014
Functional mimetics of the sialyl Lewis(X) tetrasaccharide were prepared by the enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl-Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide.
Acylated Preatroxigenin Glycosides from Atroxima congolana
2003
Six new acylated bisdesmosidic preatroxigenin saponins named atroximasaponins E1, E2 (1, 2), F1, F2 (3, 4), and G1, G2 (5, 6) were isolated as three inseparable mixtures of the trans- and cis-p-methoxycinnamoyl derivatives, from the roots of Atroxima congolana. Their structures were established through extensive NMR spectroscopic analysis as 3-O-beta-D-glucopyranosylpreatroxigenin-28-O-beta-D-xylopyranosyl-(1--4)-alpha-L-rhamnopyranosyl-(1--2)-[beta-D-glucopyranosyl-(1--3)]-[4-O-trans-p-methoxycinnamoyl]-beta-D-fucopyranoside (atroximasaponin E1, 1), and its cis-isomer, atroximasaponin E2 (2), 3-O-beta-D-glucopyranosylpreatroxigenin-28-O-beta-D-xylopyranosyl-(1--4)-alpha-L-rhamnopyranosyl-(…
Glandulosides A-D, triterpene saponins from Acanthophyllum glandulosum.
2004
Four novel triterpenoid saponins, glandulosides A (1), B (2), C (3), and D (4), together with two known saponins (5 and 6) have been isolated from the roots of Acanthophyllum glandulosum. Their structures were elucidated using a combination of homo- and heteronuclear 2D NMR techniques (COSY, TOCSY, NOESY, HSQC, and HMBC) and by FABMS. The new compounds were characterized as 23-O-beta-D-galactopyranosylgypsogenic acid-28-O-beta-D-glucopyranosyl-(1-->3)-[beta-d-galactopyranosyl-(1-->6)]-beta-D-galactopyranoside (1), 3-O-beta-D-galactopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucuronopyranosylgypsogenin-28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-l-rhamn…