Synthese anomerer Sialinsäure‐methylketoside

Kühn, Richard; Lutz, P.; MacDonald, Donald L.

doi:10.1002/cber.19660990235

Cited by 260 publications

(67 citation statements)

References 8 publications

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“…Peroxidase-conjugated rabbit anti-rat IgM (-chain specific; Zymed Laboratories Inc., South San Francisco, CA) was used for GL7, and peroxidase-conjugated goat anti-mouse IgM (-chain specific; Cappel Laboratories, Malvern, PA) was used for other antibodies. The pure synthetic ␣2-6-sialylated 6-sulfo-LacNAc determinant was synthesized by established methods from three building blocks, a sialic acid donor (27), a lactosamine donor (28), and lactosyl cholestanol with a free hydroxyl residue at CЈ-3 (29). Lactosyl cholestanol was coupled with the lactosamine donor using a catalytic amount of bis(cyclopentadienyl)hafnium(IV) dichloride-silver triflate (Cp 2 HfCl 2 -AgOTf) according to the method of Matsumoto et al (30).…”

Section: Methodsmentioning

confidence: 99%

Human B-lymphocytes Express α2-6-Sialylated 6-Sulfo-N-acetyllactosamine Serving as a Preferred Ligand for CD22/Siglec-2

Kimura

Ohmori

Miyazaki

et al. 2007

Journal of Biological Chemistry

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CD22/Siglec-2, an important inhibitory co-receptor on B-lymphocytes, is known to recognize ␣2-6-sialylated glycan as a specific ligand. Here we propose that the ␣2-6-sialylated and 6-GlcNAc-sulfated determinant serves as a preferred ligand for CD22 because the binding of a human B-cell line to CD22 was almost completely abrogated after incubating the cells with NaClO 3 , an inhibitor of cellular sulfate metabolism, and was also significantly inhibited by a newly generated monoclonal antibody specific to the ␣2-6-sialylated 6-sulfo-Nacetyllactosamine (LacNAc) determinant (KN343, murine IgM). The ␣2-6-sialylated 6-sulfo-LacNAc determinant defined by the antibody was significantly expressed on a majority of normal human peripheral B-lymphocytes as well as follicular B-lymphocytes in peripheral lymph nodes. The determinant was also expressed in endothelial cells of high endothelial venules of secondary lymphoid tissues, including lymph nodes, tonsils, and intestine-associated lymphoid tissues, more strongly than on B-lymphocytes, suggesting a role for CD22 in B-cell interaction with blood vessels and trafficking. These results indicate that the ␣2-6-sialylated 6-sulfoLacNAc determinant serves as an endogenous ligand for human CD22 and suggest the possibility that 6-GlcNAc sulfation as well as ␣2-6-sialylation may regulate CD22/Siglec-2 functions in humans.CD22/Siglec-2 (sialic acid-binding immunoglobulin-like lectins) is an important inhibitory receptor on B-lymphocytes. It controls the signaling threshold of B-cell receptors, preventing their overactivation (1-4). It has inhibitory immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic domain and regulates B-cell receptor signaling by recruiting the tyrosine phosphatase SHP-1 (Src homology 2 domain-containing protein-tyrosine phosphatase-1) (5). It is known to also affect distribution and trafficking of B-lymphocytes, such as in the homing of IgD ϩ B-lymphocytes to the bone marrow (6). Disruption of CD22 is known to result in production of high affinity autoantibodies, an increase in follicular mature B-lymphocytes, and a reduction in the number of marginal zone B-lymphocytes (7, 8).CD22/Siglec-2 is known to specifically bind to its ligand, ␣2-6-sialylated glycan (9 -12). B-lymphocytes themselves significantly express ␣2-6-sialylated glycan on their surface, which can serve as a cis-ligand for endogenous CD22, thus masking the ligand binding activity of CD22 on the majority of B-lymphocytes. CD22/Siglec-2 is proposed to exert trans-interaction with target cells expressing ␣2-6-sialylated glycans only when expression of the endogenous cis-ligand is suppressed or when the trans-ligand on target cells has a significantly higher binding activity than the cis-ligand (13,14). For better understanding of CD22 function, it is important to know the diversity of ␣2-6-sialylated glycans and to find candidate glycans that preferentially bind to CD22.In mice, it has long been known that CD22 prefers the ␣2-6-N-glycolylsialic acid terminus over the ␣2-6-N-acetylsiali...

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Section: Methodsmentioning

confidence: 99%

Human B-lymphocytes Express α2-6-Sialylated 6-Sulfo-N-acetyllactosamine Serving as a Preferred Ligand for CD22/Siglec-2

Kimura

Ohmori

Miyazaki

et al. 2007

Journal of Biological Chemistry

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“…The first 5 ml of the column effluent was discarded; the next 12.5 ml was collected, evaporated to dryness under reduced pressure on a rotary evaporator and dissolved in 1.0 ml of water for quantitation with thiobarbituric acid and/or preparation of derivatives. Methylesters were prepared using methanol and Dowex 50 x 8 H+ (12). Trimethylsilylation of the methyl esters of the sialic acid in the isolated samples was performed as described by Kamerling et al (9).…”

Section: Methodsmentioning

confidence: 99%

Alterations in Cultured Fibroblasts of Sibs with an Infantile Form of a Free (Unbound) Sialic Acid Storage Disorder

et al. 1983

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SummaryCultured fibroblasts from two sibs with generalized hypertonia, hepatosplenomegaly, and psychomotor retardation within the first year of life were found to have unusual morphologic features. When examined by phase microscopy, the unstained and unfixed cells contained a large number of vacuolated structures whose gross appearance resembled that of a honeycomb in the cell cytoplasm. Electron microscopy studies, following fixation, showed the "honeycombing" to be the result of numerous, closely packed, cytoplasmic, membrane-bound vacuoles. In some of these structures the remains of fibrillogranular material could be detected.Biochemical analysis of crude snnicates of these cells revealed increased levels (4-7 x N) of an acid soluble component that reacted with thiobarbituric acid. Analysis of trimethylsilyl derivatives of this material by gas liquid chromatography and mass spectrometry showed it to be indistinguishable from sialic acid (Nacetylneuraminic acid). Quantitation of this material from the cells of one of the sibs after isolation on a Dowex column yielded 39.8 nmoles of free (unbound) sialic acid per mg protein whereas normal fibroblasts had 1-2 nmoles per mg. Bound sialic acid levels were at the upper limits of normal (24.8 versus 11-23 nmoles per mg protein). The concentration of cytidine monophosphate-sialic acid was normal.After incubation of the patient's fibroblasts with [3H]-~-acetylmaunosamine for 72 h, there was a 7-fold increase (compared to normal fibroblasts) in the amount of radioactivity in free sialic acid present in the acid soluble fraction. The amount of labeled, bound sialic acid in the acid-insoluble pool, however, was the same in both patient and control fibroblasts. Over the past few years several clinical forms of sialidosis have been described (14). Common to each of these related disorders has been an increased accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked to a variety of oligosaccharides and/or glycoproteins. Additionally, it has been demonstrated that these alterations are associated with, and presumptively the result of, a deficiency of a lysosomal sialidase (neuraminidase) (4,20,22).We now describe the morphologic and biochemical features of fibroblasts cultured from two infants (sibs) who suffer not from a storage of "bound" sialic acid but, rather, from an increased accumulation and excretion of free sialic acid. In contrast to the sialidosis patients, these individuals have normal to above normal levels of sialidase. The clinical and/or biochemical findings in these patients clearly indicate that they suffer from a disorder distinct from either Salla disease (3, 17) or sialuria (15), both of which are also characterized by an increased accumulation and/ or excretion of unbound sialic acid. These sibs, however, do appear to have certain features in common with patients recently described by Hancock et al. MATERIALS AND METHODSCultured fibroblasts were established from skin biopsies of the patients and controls as previously ...

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“…13C NMR spectra were recorded in 10- (23). In this latter treatment the polysaccharide (1 mg) was treated with two separate additions of 50 units of the enzyme over a period of 72 hr as described (23).…”

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confidence: 99%

Structure and serology of the native polysaccharide antigen of type Ia group B Streptococcus

Jennings

Rosell

Kasper

1980

Proc. Natl. Acad. Sci. U.S.A.

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The native polysaccharide antigen isolated from type Ia group B Streptococcus by using pH-controlled growth conditions and extraction procedures contains D-alactose, D-glucose, 2-acetamido-2-deoxy-D-glucose, and sialic acid in the molar ratio of 2:1:1:1. The structure of the native type Ia antigen has been elucidated; it can be represented by the following repeating unit in which all the side-chain P-D-galactopyranose units are masked by sialic acid residues:Removal of all the sialic acid groups yields the incomplete type Ia polysaccharide antigen with exposed terminal P-D-galactopyranose residues. Antisera to type Ia organisms produced in rabbits according to the Lancefield procedures contain antibodies specific for both the native and incomplete antigens. Although sialic acid is not itself a determinant in the formation of antibodies to the native polysaccharide, it is an essential part of a larger determinant. In order to maintain the high degree of immunologic specificity of the native antigen, this determinant must be at least a trisaccharide unit, because the native polysaccharide as isolated has terminal disaccharide units [a-D-NeuAcp42-'3),B-D-Galp] identical to those found in the human M and N blood group substances and fetuin. Formation of antibodies to the incomplete antigen is due to determinants terminating in P-D-galactopyranose residues. These determinants are robably generated by the removal of the masking sialic aci residues from the cell-associated native polysaccharide by degradative processes that occur in organisms grown without pH control.

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Synthese anomerer Sialinsäure‐methylketoside

Cited by 260 publications

References 8 publications

Human B-lymphocytes Express α2-6-Sialylated 6-Sulfo-N-acetyllactosamine Serving as a Preferred Ligand for CD22/Siglec-2

Human B-lymphocytes Express α2-6-Sialylated 6-Sulfo-N-acetyllactosamine Serving as a Preferred Ligand for CD22/Siglec-2

Alterations in Cultured Fibroblasts of Sibs with an Infantile Form of a Free (Unbound) Sialic Acid Storage Disorder

Structure and serology of the native polysaccharide antigen of type Ia group B Streptococcus

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