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Haemonchus contortus is one of the most economically important parasites infecting small ruminants worldwide. This nematode has shown a great ability to develop resistance to anthelmintic drugs, calling for the development of alternative control approaches. Because lectins recognize and bind to specific carbohydrates and glycan structures present in parasites, they can be considered as an alternative to develop new antiparasitic drugs. Accordingly, this work aimed to investigate the anthelmintic effect of Canavalia brasiliensis (ConBr) lectin against H. contortus and to evaluate a possible interaction of ConBr with glycans of this parasite by molecular docking. ConBr showed significant inhibition of H. contortus larval development with an IC50 of 0.26 mg mL?1. Molecular docking assays revealed that glycans containing the core trimannoside [Man(alpha1-3)Man(alpha1-6)Man] of H. contortus interact in the carbohydrate recognition domain of ConBr with an interaction value of MDS = ?248.77. Our findings suggest that the inhibition of H. contortus larval development is directly related to the recognition of the core trimannoside present in the glycans of these parasites. This work is the first to report on the structure-function relationships of the anthelmintic activity of plant lectins.

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The efficacy of antisense oligonucleotides depends on the ability to reach in vivo their target cells. We aim to develop strategies to enhance uptake of phosphorothioate oligodeoxynucleotides by Kupffer cells. To this end, we conjugated cholesterol to ISIS-3082, a phosphorothioate oligodeoxynucleotide specific for intercellular adhesion molecule-1. The cholesterol-conjugated oligonucleotide, denoted ISIS-9388, associated readily with lactosylated low-density lipoprotein (LacLDL), a lipidic carrier that is taken up by galactose receptors on Kupffer cells. Association of up to 10 molecules of ISIS-9388 per LacLDL particle did not induce aggregation. LacLDL-associated [3H]ISIS-9388 was rapidly taken up by the liver after injection into rats (52.9 ± 1.8% of the dose within 2 min versus 18.6 ± 2.8% for ISIS-3082). N-acetylgalactosamine inhibited hepatic uptake, indicating involvement of galactose-specific receptors. Liver cells were isolated at 60 min after injection of LacLDL-associated [3H]ISIS-9388. Kupffer cells displayed the highest uptake: 88.1 ± 24.7 ng of oligonucleotide/mg of cell protein, which is 6-14 times higher than after injection of free ISIS-9388 or ISIS-3082 (15.0 ± 3.8 ng and 6.3 ± 1.4 ng, respectively). It can be calculated that Kupffer cells contribute 43.9 ± 5.4% to the liver uptake (free ISIS-9388 and ISIS-3083 14.5 ± 3.1% and 8.3 ± 3.2%, respectively). In conclusion, conjugation of a phosphorothioate oligodeoxynucleotide with cholesterol and its subsequent association with LacLDL results in a substantially increased Kupffer cell uptake of the oligonucleotide. As Kupffer cells play a key role in inflammation, our approach may be utilized to improve antisense-based therapeutic intervention during inflammation.

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The corresponding 4-substituted glycosyl thiosemicarbazide derivatives (6a-6l) were obtained by the reaction of glycosyl isothiocyanate 4 with various hydrazides. Further cyclization with the system of p-TsCl/TEA led to the formation of N-glycosyl-5-substituted 1,3,4-thiadiazole-2-amine (7a-7l). Subsequent removal of the acetyl groups were conducted using the system of NaOMe/MeOH. The chemical structures of all new products were confirmed by IR, 1H NMR and ESI-HRMS. The acetylcholinesterase (AChE) inhibitory activities of those compounds were tested by Ellman’s method. Among them, the compound 8h possessed the best acetylcholinesterase-inhibition activity with IC50 of 18.38 ± 0.89 muM.

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Terminal galactosylations of cello- and chito-oligomers are studied employing galactosyltransferase with and without alpha-lactalbumin. The lactose synthase complex allows just for galactosylation of cellobiose in lower yield but not for higher cello-oligomers. In contrast, the affinity in galactosylation of chito-oligomers increases with higher members to reach the maximum at chitohexaose with only a 30% reduction in transfer rate. In addition to kinetic data, preparative studies with a number of acceptor substrates gave galactosylated oligosaccharides in high yields. (Figure Presented). Copyright Taylor & Francis Group, LLC.

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New, multigram routes to suitably protected L-iduronyl monosaccharide donors 4 and 5 and 2-azidoglucose acceptors 6 and 7 are described. The L-iduronyl and D-glucuronyl disaccharides 1-3 were then prepared from these compounds, by means of efficient and regioselective protective group manipulations. These disaccharides form the basis of a combinatorial approach toward the synthesis of heparan sulfate fragments representative of the heterogeneous regions of this polysaccharide. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)Introduction.

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In the present report a practical and versatile procedure for the solid-phase synthesis of N-linked glycopeptides from natural sources has been demonstrated. The approach is based on the mild hydrazinolysis procedure to release N-linked oligosaccharides in their intact unreduced form from the natural glycoproteins, e.g. fetuin and ribonuclease B and subsequent formation of the corresponding glycosylamines. Treatment of the reducing sugars 1-7 with a saturated solution of ammonium hydrogen carbonate in either water or dimethyl sulfoxide (DMSO) gives in almost quantitative yields the glycosylamines 8-14. Coupling of the unprotected glycosylamines 8-14 to the side-chain-activated aspartic acid derivative Fmoc-Asp(ODhbt)-OBut 16 affords the N-glycosylated asparagine derivatives 17-23. Subsequent acetylation of the carbohydrate hydroxy groups and cleavage of the tert-Bu ester by trifluoroacetic acid (TFA) treatment yields the glycosylated N-linked building blocks 31-37. The building blocks 31-37 are then incorporated into the multiple-column peptide-synthesis protocol of the glycopeptide T-cell epitope analogues 40-46 of the mouse haemoglobin-derived decapeptide Hb (67-76), VITAFNEGLK. The decapeptide sequence VITAFNEGLK binds well to the MHC Class II Ek molecule and is non-immunogenic in CBA/J mice. Syntheses of several natural and unnatural glycosylations, e.g. N-acetylglucosamine, N,N?-diacetylchitobiose, glucose, maltotriose, maltoheptose and di- and triantennary complex oligosaccharides on the decapeptide Hb (67-76) affording the N-linked glycopeptides 40-46 are described. The N-linked glycopeptides 40-46 have been fully characterised by 1D- and 2D-1H and 13C NMR spectroscopy and by ES-MS.

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The adiabatic compressibility and partial specific volume of hen egg-white lysozyme, which were determined by the sound velocity and density measurements at 25C, decreased by addition of its inhibitors, N-acetyl-D-glucosamine oligomers, in the order of monomer > dimer > trimer. This result demonstrates that the inhibitor binding induces the atomic packing in the cleft of the active site to diminish the structural fluctuation of the protein.

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Using a crude beta-N-acetylhexosaminidase from Aspergillus oryzae both tri-N-acetylchitotriose (GlcNAc)3 (1,n=1) and tetra-N-acetylchitotetraose (GlcNAc4) (1,n=2) act respectively as both glycosyl donor and glycosyl acceptor to give product mixtures containing significant quantities of the corresponding penta- and hexasaccharides <1 (n=3) and 1 (n=4), respectively> which are readily isolated and purified by charcoal-Celite chromatography.

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The invention relates to compounds and methods for inhibiting production and function of tyrosinase in the skin of a mammal. The invention further relates to compounds and methods for inhibiting darkening of the skin of a mammal, as well as lightening the skin of a mammal and reducing pigmentation in the skin of a mammal.

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A HPLC method was developed for the determination of glucosamine in crab shells. The amount of glucosamine residue can be used to estimate the amount of chitin in analyzed material. Crab samples were hydrolysed with 6 M HCl at 100 C for 13 h and the released glucosamine was determined by HPLC using refractive index (RI) detection. Separations were performed using an ODS-2 column with an isocratic mobile phase consisting of 10% methanol, 90% hexanesulfonate, pH 2.1. Glucosamine identification was carried out not only on basis of retention time, but also with respect to mass spectra, which were acquired by HPLC-MS.

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