The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Reinhard Brossmer - One of the best experts on this subject based on the ideXlab platform.
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Specificity of the binding site of the sialic acid-binding lectin from ovine placenta, deduced from interactions with synthetic analogues
Glycoconjugate Journal, 2000Co-Authors: M. Fernanda Troncoso, M. Mercedes Iglesias, Rainer Isecke, Carlota Wolfenstein Todel, Reinhard BrossmerAbstract:The specificity of the sialic acid-binding lectin from ovine placenta was examined in detail by haemagglutination inhibition assays applying a panel of 32 synthetic sialic acid analogues. The carboxylic acid Group is a prerequisite for the interaction with the lectin, the α-anomer of the methyl glycoside is only a little more effective as an inhibitor than the β-anomer and the most potent inhibitor was 9-deoxy-10-carboxylic acid Neu5Ac, followed by 4-oxo-Neu5Ac. In contrast to the majority of known sialic acid-binding lectins, the N-Acetyl Group of Neu5Ac is not indispensable for binding, neither is the hydroxyl Group at C-9 since substitutions at this carbon atom are well tolerated. Furthermore, all sulfur-containing substituents at C-9 enhanced the affinity of the lectin. This is the first sialic acid-binding lectin found to strongly bind thio derivatives.
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Functional Groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues
European journal of biochemistry, 1998Co-Authors: Sørge Kelm, Rainer Isecke, Reinhard Brossmer, Hans-jürgen Gross, Karen Strenge, Roland SchauerAbstract:The siglecs, formerly called sialoadhesins, are a family of I-type lectins binding to sialic acids on the cell surface. Five members of this family have been identified: sialoadhesin, myelin-associated glycoprotein (MAG), Schwann cell myelin protein (SMP), CD22 and CD33. We have investigated the relevance of substituents at position C-9 and in the N-Acetyl Group of N-Acetylneuraminic acid, using a series of synthetic sialic-acid analogues either on resialylated human erythrocytes or as free A-glycosides in hapten inhibition. All five siglecs require the hydroxy Group at C-9 for binding, suggesting hydrogen bonding of this substituent with the binding site. Remarkable differences were found among the proteins in their specificity for modifications of the N-Acetyl Group. Whereas sialoadhesin, MAG and SMP do not tolerate a hydroxy Group as in N-glycolylneuraminic acid, they bind to halogenated acetyl residues. In the case of MAG, N-fluoroacetylneuraminic acid is bound about 17-fold better than N-Acetylneuraminic acid. In contrast, human and murine CD22 both show good affinity for N-glycolylneuraminic acid, but only human CD22 bound the halogenated compounds. In conclusion, our data indicate that interactions of the hydroxy Group at position 9 and the N-acyl substituent contribute significantly to the binding strength.
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A lectin from the Asian horseshoe crabTachypleus tridentatus: purification, specificity and interaction with tumour cells
Glycoconjugate Journal, 1994Co-Authors: Edgar Fischer, Nguyen Quoc Khang, Ghislaine Letendre, Reinhard BrossmerAbstract:A lectin from the haemolymph of the Asian horseshoe crab Tachypleus tridentatus was purified to homogeneity by affinity chromatography on Sepharose 4B-bound N -acetylneuraminic acid. The specificity of this lectin was studied by haemagglutination inhibition with sialic acid analogues, N -acetylhexosamines and glycoproteins. For the interaction with the agglutinin the N -acetyl Group and the glyceryl side chain of N -acetylneuraminic acid are important, while presence of an aglycon, specially an α-glycosidically linked lactose increases affinity to the lectin. The strongest glycoprotein inhibitors were ovine as well as bovine submaxillary mucin and Collocalia mucin, all being O -chain glycoproteins but carrying completely different carbohydrate chains. The majority of N -chain proteins were inactive. As the lectin agglutinates human erythrocytes, but not the murine lymphoma lines Eb and ESb or the human colon carcinoma HT 29, these cancer cells apparently lack the ‘ Tachypleus tridentatus agglutinin-receptor’ which is present on red cells and O -chain glycoproteins.
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methyl α glycoside of n thioacetyl d neuraminic acid a potential inhibitor of influenza a virus a 1h nmr study
FEBS Letters, 1993Co-Authors: Daisy Machytka, Rainer Isecke, Reinhard Brossmer, Igor Kharitonenkov, Peter Hetterich, Roger A Klein, Hansdieter Klenk, Heinz EggeAbstract:The binding of influenza A virus hemagglutinin to its cell surface receptor, α-linked 5-N-Acetylneuraminic acid (sialic acid), was studied in solution. The effect of structural modifications introduced into the N-Acetyl Group of the sialic acid on the binding was monitored by determining the dissociation constants by proton nuclear magnetic resonance (1H NMR) spectroscopy. Methyl α-glycoside of N-thioacetylneuraminic acid showed high, whereas the corresponding N-methylcarbamoylneuraminic acid exhibited relatively low binding affinity towards the hemagglutinin.
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Use of sialic acid analogues to define functional Groups involved in binding to the influenza virus hemagglutinin
European journal of biochemistry, 1992Co-Authors: Sørge Kelm, Reinhard Brossmer, James C. Paulson, Ursula Rose, Walther Schmid, Babasaheb P. Bandgar, Erwin Schreiner, Michael Hartmann, Erich ZbiralAbstract:The initial step of influenza infection is binding of the virus particles via their hemagglutinin to cell-surface sialic acids. This study was initiated to elucidate the functional Groups of the nine-carbon sialic acid molecule which interact with the hemagglutinin and contribute to the affinity of this sugar to the protein. In order to address this question, synthetic sialic acid analogues were tested in a virus adsorption inhibition assay for their inhibitory potency. Modifications in three regions of the sialic acid molecule were evaluated: the glycerol side chain (C7-C9), the N-Acetyl Group at C5, and the carboxy Group (C1). In the glycerol side chain, the hydroxy Groups at C7 and C8 appear to be important for binding through hydrogen bonds, whereas the hydroxyl at C9 does not appear to be involved. The N-Acetyl Group is critical for the interaction of sialic acid with the hemagglutinin. The results suggest that its contribution is mediated through hydrophobic interactions of the methyl Group. Finally, the orientation of the carboxy Group is essential for the binding of sialic acid to the hemagglutinin. The information gained in this study will be useful in developing novel compounds which bind more avidly to the influenza virus hemagglutinin. Such a strategy may contribute to the design of new anti-influenza drugs.
Adam Liwo - One of the best experts on this subject based on the ideXlab platform.
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The Photophysics of β-Tyrosine and Its Simple Derivatives
Journal of Fluorescence, 1997Co-Authors: Wieslaw Wiczk, Leszek Łankiewicz, Cezary Czaplewski, Stanislaw Oldziej, Krystyna Stachowiak, Alicja Michniewicz, Beata Micewicz, Adam LiwoAbstract:Synthesis and photophysical studies of ( O -methyl)-β-tyrosine (β-tyrosine; an analogue of tyrosine, in which the amino Group is moved from the α- to the β-carbon, closer to the phenol ring) and its derivatives with a blocked amino and/or carboxyl Group were performed to explain the nature of the fluorescence of tyrosine derived analogues. All β-tyrosine derivatives, except Ac-βTyr(Me), displayed the monoexponential fluorescence decay. The biexponential fluorescence decay observed for Ac-βTyr(Me) is assumed to be the result of the presence of two low-energy conformations (extended and with an intramolecular hydrogen bond). Higher quenching of the fluorescence of β-tyrosine derivatives by the N -acetyl Group than by the N -methylamide Group moved farther was found, contrary to the data found for the respective derivatives of natural tyrosine. The obtained photophysical data are discussed with theoretical calculations (AMBER, AM1) on the basis of the rotamer model.
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The photophysics of β-homo-tyrosine and its simple derivatives
Journal of Photochemistry and Photobiology A: Chemistry, 1996Co-Authors: Wieslaw Wiczk, Leszek Łankiewicz, Cezary Czaplewski, Krystyna Stachowiak, Alicja Michniewicz, Stanisław Ołdziej, Adam LiwoAbstract:Synthesis and photophysical studies of (O-methyl)-β-tyrosine (β-tyrosine; an analogue of tyrosine, in which the amino Group is moved from the α- to the β-carbon, closer to the phenol ring) and its derivatives with a blocked amino and/or carboxyl Group were performed to explain the nature of the fluorescence of tyrosine derived analogues. All β-tyrosine derivatives, except Ac-βTyr(Me), displayed the monoexponential fluorescence decay. The biexponential fluorescence decay observed for Ac-βTyr(Me) is assumed to be the result of the presence of two low-energy conformations (extended and with an intramolecular hydrogen bond). Higher quenching of the fluorescence of β-tyrosine derivatives by the N-Acetyl Group than by the N-methylamide Group moved farther was found, contrary to the data found for the respective derivatives of natural tyrosine. The obtained photophysical data are discussed with theoretical calculations (AMBER, AM1) on the basis of the rotamer model.
David Bonnaffe - One of the best experts on this subject based on the ideXlab platform.
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synthesis of glycosaminoglycan oligosaccharides an unexpected inhibitory effect of a remote n acetyl Group upon trichloroacetimidate mediated couplings
European Journal of Organic Chemistry, 2004Co-Authors: Ricardo Lucas, Daniel Hamza, Andre Lubineau, David BonnaffeAbstract:In order to prepare biologically relevant heparan sulfate (HS) tetrasaccharide fragments containing an N-Acetylated glucosamine at the reducing end, we studied the glycosylation reaction between the 2-azidoglucose trichloroacetimidate disaccharide donor 1 and a range of 4′-OH-uronyl disaccharide acceptors with an N-Acetylglucosamine at the reducing terminus. Although we tried several condensation conditions, no tetrasaccharide was formed. We show that the failure of these reactions is due to the presence of the N-Acetyl Group, which inhibits the trichloroacetimidate-mediated glycosylation, since the analogous reaction proceeds smoothly once the N-Acetyl Group has been replaced by an azide. In the latter case, we show that the careful optimisation of the solvent system is a powerful way to obtain high yields and α-stereoselectivity in coupling reactions of 1 with the 4-OH of a GlcUA acceptor. Thus, in a THF/Et2O (9:1) system, we obtained the GlcUA-β-(1→4)-GlcN3-α-(1→4)-GlcUA-β-(1→4)-GlcN3 tetrasaccharide 16α/β in 90% isolated yield and 92:8 α/β ratio, as compared to 57% yield and 70:30 α/β ratio when CH2Cl2 was used. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
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Synthesis of Glycosaminoglycan Oligosaccharides − An Unexpected Inhibitory Effect of a Remote N‐Acetyl Group upon Trichloroacetimidate‐Mediated Couplings
European Journal of Organic Chemistry, 2004Co-Authors: Ricardo Lucas, Daniel Hamza, Andre Lubineau, David BonnaffeAbstract:In order to prepare biologically relevant heparan sulfate (HS) tetrasaccharide fragments containing an N-Acetylated glucosamine at the reducing end, we studied the glycosylation reaction between the 2-azidoglucose trichloroacetimidate disaccharide donor 1 and a range of 4′-OH-uronyl disaccharide acceptors with an N-Acetylglucosamine at the reducing terminus. Although we tried several condensation conditions, no tetrasaccharide was formed. We show that the failure of these reactions is due to the presence of the N-Acetyl Group, which inhibits the trichloroacetimidate-mediated glycosylation, since the analogous reaction proceeds smoothly once the N-Acetyl Group has been replaced by an azide. In the latter case, we show that the careful optimisation of the solvent system is a powerful way to obtain high yields and α-stereoselectivity in coupling reactions of 1 with the 4-OH of a GlcUA acceptor. Thus, in a THF/Et2O (9:1) system, we obtained the GlcUA-β-(1→4)-GlcN3-α-(1→4)-GlcUA-β-(1→4)-GlcN3 tetrasaccharide 16α/β in 90% isolated yield and 92:8 α/β ratio, as compared to 57% yield and 70:30 α/β ratio when CH2Cl2 was used. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Gabi Baisch - One of the best experts on this subject based on the ideXlab platform.
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Glycosyltransferase catalyzed assemblage of sialyl-Lewisa-saccharopeptides
Carbohydrate Research, 1998Co-Authors: Gabi Baisch, Reinhold ÖhrleinAbstract:Abstract A series of methyl hexopyranosiduronic acids are coupled to type I disaccharide amines to give ‘trisaccharides’ which have the natural N -acetyl Group of the type I disaccharides replaced by uronic acids (→ saccharopeptides). These saccharopeptides are surprisingly good substrates for α -2,3-sialyltransferase and fucosyltransferase III. The enzymes transfer N -acetylneuraminic acid and fucose, respectively, onto these acceptor substrates, despite the far reaching alterations, regio- and stereospecifically in the expected manner to yield sialyl-Lewis a -saccharopeptides.
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Enzymatic synthesis of sialyl-Lewisa-libraries with two non-natural monosaccharide units
Bioorganic & medicinal chemistry letters, 1998Co-Authors: Gabi Baisch, Reinhold Öhrlein, Markus Streiff, Frank KolbingerAbstract:Abstract A series of sialylated type-I sugars, which have the natural N-Acetyl Group of the glucosamine moiety replaced by a wide range of amides, is incubated with recombinant fucosyl-transferase III and non-natural guanosine-diphosphate activated donor-sugars. Surprisingly, the enzyme tolerates the simultaneous alterations on the donor and acceptor to form a wide array of sialyl-Lewisa-analogues.
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Enzymatic fucosylations of non-natural sialylated type-I trisaccharides with recombinant fucosyl-transferase-III
Bioorganic & medicinal chemistry letters, 1998Co-Authors: Gabi Baisch, Reinhold Öhrlein, Markus StreiffAbstract:Abstract Recombinant fucosyl-transferase-III (Lewis type enzyme) is used to prepare a series of non-natural sialyl-Lewis a derivatives on a preparative scale. The enzyme tolerates a wide range of acceptors which have the natural N-Acetyl Group of the glucosamine moiety replaced by substituted aromatic and hetero-aromatic amides.
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Enzymatic galactosylation of non-natural glucosamide-acceptors
Bioorganic & Medicinal Chemistry Letters, 1996Co-Authors: Gabi Baisch, Reinhold Öhrlein, Beat ErnstAbstract:Abstract Commercial galactosyltransferase is used to galactosylate non-natural glucosamine derivatives. The enzyme tolerates various replacements of the natural N-Acetyl Group including charged and sulfonamide residues.
Reinhold Öhrlein - One of the best experts on this subject based on the ideXlab platform.
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Glycosyltransferase catalyzed assemblage of sialyl-Lewisa-saccharopeptides
Carbohydrate Research, 1998Co-Authors: Gabi Baisch, Reinhold ÖhrleinAbstract:Abstract A series of methyl hexopyranosiduronic acids are coupled to type I disaccharide amines to give ‘trisaccharides’ which have the natural N -acetyl Group of the type I disaccharides replaced by uronic acids (→ saccharopeptides). These saccharopeptides are surprisingly good substrates for α -2,3-sialyltransferase and fucosyltransferase III. The enzymes transfer N -acetylneuraminic acid and fucose, respectively, onto these acceptor substrates, despite the far reaching alterations, regio- and stereospecifically in the expected manner to yield sialyl-Lewis a -saccharopeptides.
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Enzymatic synthesis of sialyl-Lewisa-libraries with two non-natural monosaccharide units
Bioorganic & medicinal chemistry letters, 1998Co-Authors: Gabi Baisch, Reinhold Öhrlein, Markus Streiff, Frank KolbingerAbstract:Abstract A series of sialylated type-I sugars, which have the natural N-Acetyl Group of the glucosamine moiety replaced by a wide range of amides, is incubated with recombinant fucosyl-transferase III and non-natural guanosine-diphosphate activated donor-sugars. Surprisingly, the enzyme tolerates the simultaneous alterations on the donor and acceptor to form a wide array of sialyl-Lewisa-analogues.
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Enzymatic fucosylations of non-natural sialylated type-I trisaccharides with recombinant fucosyl-transferase-III
Bioorganic & medicinal chemistry letters, 1998Co-Authors: Gabi Baisch, Reinhold Öhrlein, Markus StreiffAbstract:Abstract Recombinant fucosyl-transferase-III (Lewis type enzyme) is used to prepare a series of non-natural sialyl-Lewis a derivatives on a preparative scale. The enzyme tolerates a wide range of acceptors which have the natural N-Acetyl Group of the glucosamine moiety replaced by substituted aromatic and hetero-aromatic amides.
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Enzymatic galactosylation of non-natural glucosamide-acceptors
Bioorganic & Medicinal Chemistry Letters, 1996Co-Authors: Gabi Baisch, Reinhold Öhrlein, Beat ErnstAbstract:Abstract Commercial galactosyltransferase is used to galactosylate non-natural glucosamine derivatives. The enzyme tolerates various replacements of the natural N-Acetyl Group including charged and sulfonamide residues.
