|Budget Amount *help
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1988: ¥4,900,000 (Direct Cost: ¥4,900,000)
The ganglioside is a group of sialic acid containing glycosphingolipid, which is mainly located in ce2.1 membranes. This project aimed to elucidate new biological functions of the ganglioside. Following results were obtained during the term of the project.
1) A new simple and improved method for fractionation and isolation of brain ganglioside species was developed. This method is based on the mapping the ganglioside species by chromatography using a new anion exchange beads (Q-sepharose).
2) Several monoclonal antibodies recognizing sugar sequence of ganglioside such as sialylparagloboside (IV^3euAcnLc4Cer), GM3(NeuAc), C-series polysialogangioside (GT3m GDlb, etc), and GMlb have been developed, and the antigenic epitopes were identified. One of them (NS24, it recognizes NeuAcalpha2-3Galbeta1-4GlcNAcbeta1-) expressed in human gastric cancer cells and also fetal gastric cells at specific stage. Therefore, NS24 may recognize specifically onco-developemental antigen.
3) Several new biologic
al functions of gangliosides were revealed. The new receptor gangliosides (IV^3NeuAcnLc4Cer, I- and i-active gangliosides, GM3, and GMlb) of human and animal influenza viruses and related paramyxo-virus were identified using several newly developed assay methods.
4.) A new developmental antigen, 0-acetylated GT3 ganglioside was identified in the fetal rat cerebral cortex.
5) Altered expression of gangliosides, especially the decrease of A-series ganglioside was identified in BALB/3T3 cells transformed by ras (viral K-, H- and cellular H-ras) oncogenes.
6) Single-amino-acid substitution in an antigenic site of influenza virus hemagglutinin can alter the specificity of binding to cell membrane-associated gangliosides.
7) A new extremely minor ganglioside, GMlb and GDlalpha were isolated from bovine brain, and the biological functions were characterized. GMlb ganglioside was identified as a developmental antigen in chick brain.
8) Ganglioside analog containing thio-glycoside linkage were synthesized and characterized as a new competitive inhibitors for influenza virus sialidase.
9) The synthase of melanoma-associated ganglioside antigen GM3, alpha2-3Gal sialyltransferase was partially purified and characterized.
10)Some protein kinases, such as Ca^<++>/carmodulin dependent protein kinase II activity was modulated by gangliosides.
ll)A new ganglioside analogs which inhibit the infection and syncitium formation by human mmunodeficiency virus were developed. Less