Structure of the Tay-Sachs' Ganglioside. I<sup>*</sup>

Ledeen, Robert W.; Salsman, Kenneth

doi:10.1021/bi00886a040

Cited by 136 publications

(26 citation statements)

References 33 publications

(30 reference statements)

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“…Moreover, the presence of a strong interaction between the PGalNAc and the NeuNAc residue has been shown by attempts to remove the sialic acid enzymatically or by mild acid hydrolysis of Cad glycophorin: the sialic acid proved to be resistant to Vibrio cholerue and Clostridium perfringens neuraminidases [23] as well as to a treatment with 20mM HCI (Piller, F., unpublished results) under conditions which removed 95% of the NeuNAc from the glycophorin A control. An identical interaction had been reported for GMZ which carries the same terminal trisaccharide [26]. As expected, all the lectins tested in this study agglutinate the Cad red blood cells and the titers do not change significantly after sialidase treatment.…”

Section: Resultssupporting

confidence: 89%

Comparison of the carbohydrate‐binding specificities of seven N‐acetyl‐D‐galactosamine‐recognizing lectins

Piller

Cartron

1990

European Journal of Biochemistry

125

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Seven plant lectins, Dolichos bijlorus agglutinin (DBA), Grijjfonia simplicifolia agglutinin (GSA, isolectin A4), Helix pomatia agglutinin (HPA), soybean (Glycine max) agglutinin (SBA), Salvia sclarea agglutinin (SSA), Vicia villosa agglutinin (VVA, isolectin B4) and Wistariafloribunda agglutinin (WFA), known to be specific for N-acetyl-D-galactosamine-(GalNAc) bearing glycoconjugates, have been compared by the binding of their radiolabelled derivatives, to eight well-characterized synthetic oligosaccharides immobilized via a spacer on an inert silica matrix (Synsorb). The eight oligosaccharides included the Forssman, the blood group A and the T antigens, as well as ctGalNAc coupled directly to the support (Tn antigen) and also structures with GalNAc linked a or /3 to positions 3 or 4 of an unsubstituted Gal. The binding studies clearly distinguished the lectins into aGalNAc-specific agglutinins like DBA, GSA and SSA, and lectins which recognize a-as well as P-linked GalNAc residues like HPA, VVA, WFA and SBA. HPA was the only lectin which bound to the P G a l l -+ 3aGalNAc-Synsorb adsorbent (T antigen) indicating that it also recognizes internal GalNAc residues. Among the aGalNAc-specific lectins, DBA strongly recognized blood group A structures while GSA displayed weaker recognition, and SSA bound only slightly to this affinity matrix. In addition, DBA and SSA were able to distinguish between GalNAc linked a1 -+ 3 and GalNAc linked a1 -+ 4, to the support, the latter being a much weaker ligand.These results were corroborated by the binding of the lectins to biological substrates as determined by their hemagglutination titers with native and enzyme-treated red blood cells carrying known GalNAc determinants, e.g. blood group A, and the Cad and Tn antigens. For SSA, the binding to the ctGalNAc matrix was inhibited by a number of glycopeptides and glycoproteins confirming the strong preference of this lectin for aGalNAc-Ser/ Thr-bearing glycoproteins.N-Acetyl-D-galactosamine (GalNAc) is an important constituent of the carbohydrate moieties of glycoproteins and glycolipids. Carbohydrate-binding proteins (lectins) which recognize this sugar residue were among the first to be studied in detail since these lectins were shown to agglutinate specifically blood group A erythrocytes ([l] binding of oligosaccharides having a terminal ct or PGalNAc linked in different positions to a or BGal, or a or PGalNAc. Some of these lectins have been used in immunocytochemistry since they are thought to bind specifically to defined carbohydrate structures (reviewed in [12]). Therefore it is of interest to compare, in the same analytical system, the binding specificities of lectins with similar recognition patterns in order to be able to choose the most appropriate lectin for a given purpose.Recently, two lectins have been purified from the seeds of Vicia villosa (VVA, isolectin B4) [13] and Salvia sclarea (SSA) [14] which were described as aGalNAc-specific and most interestingly both appeared to have a strong preference for the a...

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Section: Resultssupporting

confidence: 89%

Comparison of the carbohydrate‐binding specificities of seven N‐acetyl‐D‐galactosamine‐recognizing lectins

Piller

Cartron

1990

European Journal of Biochemistry

125

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“…et al [7]. Tay-Sachs ganglioside (GM2) was puri fied from beef brain ganglioside mixture by col umn chromatography on Anasil S (silicic acid) [5]. the p phenotype.…”

Section: B Gangliosidesmentioning

confidence: 99%

Abnormal Glycolipid Composition of Erythrocytes with a Weak P Antigen

et al. 1978

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The erythrocytes of a normal man were agglutinated more weakly than normal cells by several anti-P(1)OO^k sera, and exhibited a decreased capacity to absorb these antibodies. Analysis of his erythrocyte glycosphingolipids revealed that the globoside (P antigen) content was less than 25% of normal, and trihexosyl ceramide (the Pk antigen) was 30-40% of normal. The ganglioside content of his erythrocytes was approximately four times normal and sialosylparagloboside was increased about sixfold. It appears that his erythrocytes are unable to synthesize normal quantities of trihexosyl ceramide, and that these serological and chemical features constitute a new phenotype in the P blood group system.

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“…The resistance of the alpha-2,3-linked sialic acid from the gangliosides GM1a and GM2 to sialidase digestion has been related to the steric hindrance of the sialic acid residue by the substituent on the axial hydroxyl group at position 4 of the galactose residue [36]. Addition of bile salts to the enzymatic reaction mixture reduced the steric impediment and induced the digestion by sialidases of the alpha-2,3 bound sialic acid to the inner galactose in GM1a and GM2 gangliosides [33].…”

Section: Resultsmentioning

confidence: 99%

Specific Synthesis of Neurostatin and Gangliosides O-Acetylated in the Outer Sialic Acids Using a Sialate Transferase

et al. 2012

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Gangliosides are sialic acid containing glycosphingolipids, commonly found on the outer leaflet of the plasma membrane. O-acetylation of sialic acid hydroxyl groups is one of the most common modifications in gangliosides. Studies on the biological activity of O-acetylated gangliosides have been limited by their scarcity in nature. This comparatively small change in ganglioside structure causes major changes in their physiological properties. When the ganglioside GD1b was O-acetylated in the outer sialic acid, it became the potent inhibitor of astroblast and astrocytoma proliferation called Neurostatin. Although various chemical and enzymatic methods to O-acetylate commercial gangliosides have been described, O-acetylation was nonspecific and produced many side-products that reduced the yield. An enzyme with O-acetyltransferase activity (SOAT) has been previously cloned from the bacteria Campylobacter jejuni. This enzyme catalyzed the acetylation of oligosaccharide-bound sialic acid, with high specificity for terminal alpha-2,8-linked residues. Using this enzyme and commercial gangliosides as starting material, we have specifically O-acetylated the gangliosides’ outer sialic acids, to produce the corresponding gangliosides specifically O-acetylated in the sialic acid bound in alpha-2,3 and alpha-2,8 residues. We demonstrate here that O-acetylation occurred specifically in the C-9 position of the sialic acid. In summary, we present a new method of specific O-acetylation of ganglioside sialic acids that permits the large scale preparation of these modified glycosphingolipids, facilitating both, the study of their mechanism of antitumoral action and their use as therapeutic drugs for treating glioblastoma multiform (GBM) patients.

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Structure of the Tay-Sachs' Ganglioside. I^*

Cited by 136 publications

References 33 publications

Comparison of the carbohydrate‐binding specificities of seven N‐acetyl‐D‐galactosamine‐recognizing lectins

Comparison of the carbohydrate‐binding specificities of seven N‐acetyl‐D‐galactosamine‐recognizing lectins

Abnormal Glycolipid Composition of Erythrocytes with a Weak P Antigen

Specific Synthesis of Neurostatin and Gangliosides O-Acetylated in the Outer Sialic Acids Using a Sialate Transferase

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Structure of the Tay-Sachs' Ganglioside. I*

Cited by 136 publications

References 33 publications

Comparison of the carbohydrate‐binding specificities of seven N‐acetyl‐D‐galactosamine‐recognizing lectins

Comparison of the carbohydrate‐binding specificities of seven N‐acetyl‐D‐galactosamine‐recognizing lectins

Abnormal Glycolipid Composition of Erythrocytes with a Weak P Antigen

Specific Synthesis of Neurostatin and Gangliosides O-Acetylated in the Outer Sialic Acids Using a Sialate Transferase

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Structure of the Tay-Sachs' Ganglioside. I^*