Ganglioside GT1b, Human (Trisialoganglioside GT1b)

Nomenclature: Acetylneuraminylgalactosyl-N-acetylgalactosaminyl [N-acetylneuraminyl- N-acetylneuraminyl] galactosylglucosylceramide]\n\nGangliosides, specialized sialic acid-containing glycolipids found abundantly in the outer\nleaflet of the neural phospholipid bilayer membrane, have a profound effect on tumor cells\nwhich prompts investigation. Mammalian tumors have exhibited drastic abnormalities in\nganglioside profile. Gangliosides of normal murine neural tissue and murine neural tumor\ntissue were extracted through dissolution in both chloroform:methanol- and water-based\nsolutions, isolated using Folch partitioning of polar lipids and non-polar lipids, and purified\nusing ion exchange chromatography and desalting procedures. Ganglioside content was\nquantified using a Resorcinol assay, yielding a drastic disparity between normal neural tissue\nand tumor tissue. The distribution of specific gangliosides in the samples were analyzed using\nhigh performance thin-layer chromatography, showing a greater proportion of the more\nstructurally complex gangliosides (e.g., GD1a, GT1b) in the healthy murine neural tissue\nand a greater proportion of the structurally simple gangliosides (e.g., GM3) in the murine\nneural tumor tissue. These results suggest a role of gangliosides in tumor proliferation and\nthe possible use of the ganglioside profile as a diagnostic tool in cancer therapy.\n\nMammalian tumors have been found to exhibit abnormalities in general ganglioside\ncontent and distribution. Current research suggests gangliosides found in murine tumor\ncells may characteristically have an alternate sialic acid component. The primary sialic\nacid present in healthy murine neural tissue is N-acetylneuraminic acid (NANA). Murine\ntumor tissue on the other hand has an abundance of the alternate sialic acid form, N-\nglycolylneuraminic acid (NGNA). Although NGNA-containing gangliosides have been found\nin non-neural murine tissue, they are generally absent in healthy murine neural tissue [4].\nUntil recently, it was not clear whether the NGNA-containing gangliosides in the tumor tissue\narose from altered sialic acid caused by malignant transformation or by non-neural cellular\ncomponents. A recent study has shown that there is an enzymatic conversion from the pri-\nmary NANA-based ganglioside to the NGNA-based ganglioside. This conversion is catalyzed\nby the cytosolic enzyme NeuAc-H, which was expressed more heavily in murine tumor tissue\nthan healthy murine tissue. Current research in this field is investigating NeuAC-H regula-\ntion of the transformation of NANA-based gangliosides to NGNA-based gangliosides in the\nhopes of determining new targets for anti-tumor therapy [1].\n\nThere are five major gangliosides in the brain: GM1, GD1a, GD1b, GT1b, and GQ1b.\nThese consist of two main components: a hydrophobic ceramide unit, which anchors the ganglioside to the plasma membrane, and a hydrophilic oligosaccharide chain, to which one\nor more characteristic sialic acid groups (e.g., N-acetylneuraminic acid, N-glycolylneuraminic\nacid) are attached (see Figure 1) [3]. We chose to investigate the expression of these various\ntypes of gangliosides in murine neural tumor tissue and healthy murine neural tissue. Our\nresearch confirms our hypothesis that there is indeed a disparity of content and distribution.\nBy studying the differences in ganglioside content and distribution in healthy murine neural\ntissue and murine neural tumor tissue, we may be more capable of discovering new diagnostic\nand preventative measures in cancer therapy.\n\nAbbreviations Used:\nNANA-N-acetylneuraminic acid\nNGNA-N-glycolyneuraminic acid\nSA-sialic acid\nGM-monosialoganglioside (only 1 sialic acid branch (NANA or NGNA) off oligosaccharide chain)\nGD-disialoganglioside (2 sialic acid branches of oligosaccharide chain)\nGT-trisialoganglioside (3 sialic acid brances of oligosaccharide chain)\nGQ-quadrasialoganglioside (4 sialic acid branches of oligosaccharide chain)

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SPECIFICATIONS

Catalog Number

G2006-80

Size

1mg

Form

Supplied as a lyophilized powder from chloroform-methanol solution.

Purity

Purified by HPLC, >98% (TLC)

References

1. Ecsedy J. A., Manfredi M. G., Yohe H. C., and Seyfried T. N.: Ganglioside Biosynthesis Gene Expression in Experimental Mouse Brain Tumors. Cancer Research. (Vol. 57, 15 April 1997): 1580-3. 2. El-Abbadi M. and Seyfried T. N.: Influence of Growth Environment on the Ganglio-side Composition of an Experimental Mouse Brain Tumor. Molecular and Chemical Neuropathology. (Vol. 21, 1994): 273-85. 3. Ledeen, Robert W.: The Chemistry of Gangliosides. Journal of the American Oil Chemists