2003 Fiscal Year Annual Research Report

新しい生理活性複合糖質の発見と機能に関する基礎的研究

Research Project

Project/Area Number	12306007
Research Institution	Gifu University
Principal Investigator	木曽真岐阜大学, 農学部, 教授 (90092931)
Co-Investigator(Kenkyū-buntansha)	安藤進東京都老人総合研究所, 生体膜部門, 副所長(研究職) (30073000) 神奈木玲児愛知がんセンター, 病理学第二部, 部長(研究職) (80161389) 石田秀治岐阜大学, 農学部, 助教授 (20203002)
Keywords	セレクチン / ガングリオシド / シアル酸 / シアリルルイスX / シアリルルイスA / シグレック / CD38 / 糖脂質
Research Abstract	(1)我々の独創的研究により発見されたシアリル6-スルホルイスXを起点とするL-セレクチンのリガンドプロセッシングには、シアル酸のデーN-アセチル化による活性化とラクタム化による不活性化が重要な鍵反応であることを、系統的な精密合成により初めて分子レベルで証明した(Carbohydr.Res.,338,2793-2812,2003)。すなわち、ラクタム化ノイラミン酸を含む六糖性シアリル6-O-スルホルイスXガングリオシド及びシアリル6-O-スルホパラグロボシドの高効率的完全合成に成功した。これら合成ガングリオシドプローブを用いることにより、ラクタム化シアリル6-O-スルホルイスXが、G159モノクローナル抗体によって認識される主要抗原決定基の一つであることを明らかにした。 (2)α-系列ハイブリッド型ガングリオシドをリード化合物とした新規硫酸化ガングリオシドGSC-338が、神経シグレックの一つであるミエリン関連糖タンパク質MAGの高親和性リガンドである(Carbohydr.Res.,338,1621-1639,2003)ことを発見すると同時に、白血球表面抗原CD38のNADase活性を強力に阻害する新規物質であることを初めて明らかにした(Bioorg.Med.Chem.Lett.,13,3441-3445,2003)。 (3)癌関連抗原として予測されていたα-(2-3)/α-(2-6)-ジシアリルラクトテトラオシルセラミドおよびジシアリルLewis Aガングリオシドの全合成に成功し(Carbohydr.Res.,338,503-514,2003)、その生合成経路を明らかにするとともに、予想どおり癌関連抗原として機能することを分子レベルで解明した(J.Biol.Chem.,278,22787-22794,2003)。

Research Products
(14 results)

All Other

All Publications (14 results)

[Publications] Hamada, T.: "NMR structure elucidation of cyclic sialyl 6-sulfo Lewis x, a biologically dormant form of L-selectin ligand"Tetrahedron Lett.. 44. 1167-1170 (2003)
[Publications] Ando, T.: "First total synthesis of α-(2-3)/α-(2-6)-disialyl lactotetraosyl ceramide and disialyl Lewis A ganglioside as cancer-associated carbohydrate antigens"Carbohydr.Res.. 338. 503-514 (2003)
[Publications] Ito, H.: "Systematic synthesis and MAG-binding activity of novel sulfated GM1b analogues as the mimics of Chol-1 (α-series) gangliosides : highly active ligands for neural siglecs"Carbohydr.Res.. 338. 1621-1639 (2003)
[Publications] Imamura, A.: "Di-tert-butylsilylene (DTBS) group-directed α-selective galactosylation unaffected by C-2 participating functionalities"Tetrahedron Lett.. 44. 6725-6728 (2003)
[Publications] Tsuchida, A.: "Synthesis of disialyl Lewis a (Le^a) structure in colon cancer cell lines by a sialyltransferase, ST6GalNAc VI, responsible for the synthesis of α-series ganglios"J.Biol.Chem.. 278. 22787-22794 (2003)
[Publications] Ando, H.: "Extending of the possibility of N-Troc-protected sialic acid donor toward variant sialo-glycoside synthesis"Tetrahedron Lett.. 44. 6883-6886 (2003)
[Publications] Hori, K.: "Synthetic study on Campylobacter jejuni lipopolysaccharides : an improved synthesis of a branched, heptose-containing trisaccharide core structure and its conversion into ganglioside GD3-related hexasaccharide"Eur.J.Org.Chem.. 3752-3760 (2003)
[Publications] Hara-Yokoyama, M.: "Novel sulfated gangliosides, high affinity ligands for neural siglecs, inhibit NADase activiy of leukocyte cell surface antigen CD38"Bioorg.Med.Chem.Lett.. 13. 3441-3445 (2003)
[Publications] Tamai, R: "Cell activation by monosaccharide lipid A analogues utilizingt Toll-like receptor 4"Immunology. 110. 66-72 (2003)
[Publications] Yamaguchi, M.: "Studies on the endogenous L-selectin ligands : Systematic and highly efficient total synthetic routes to lactamized-sialyl 6-O-sulfo Lewis x and other novel gangliosides containing lactamized neuraminic acid"Carbohydr.Res.. 338. 2793-2812 (2003)
[Publications] Ishihara, A.: "Synthesis and selectin-blocking activity of a novel analog of sulfatide : 3-C-carboxymethyl-galactosyl lipids"J.Carbohydr.Chem.. 22. 513-520 (2003)
[Publications] Fukunaga, K.: "Synthesis of lacto- and neolacto-series an ganglioside analogs containing N-glycolylneuraminic acid : probes for investigation of specific receptor structures recognized by influenza A viruses"J.Carbohydr.Chem.. 22. 919-937 (2003)
[Publications] Ando, H.: "Best Synthetic Methods : Carbohydrates"Elsevier. 430 (2003)
[Publications] 鈴木康夫: "コールドスプリングハーバー糖鎖生物学"丸善. 527 (2003)

2003 Fiscal Year Annual Research Report

新しい生理活性複合糖質の発見と機能に関する基礎的研究

Principal Investigator

木曽 真 岐阜大学, 農学部, 教授 (90092931)

Research Products

[Publications] Hamada, T.: "NMR structure elucidation of cyclic sialyl 6-sulfo Lewis x, a biologically dormant form of L-selectin ligand"Tetrahedron Lett.. 44. 1167-1170 (2003)

[Publications] Ando, T.: "First total synthesis of α-(2-3)/α-(2-6)-disialyl lactotetraosyl ceramide and disialyl Lewis A ganglioside as cancer-associated carbohydrate antigens"Carbohydr.Res.. 338. 503-514 (2003)

[Publications] Ito, H.: "Systematic synthesis and MAG-binding activity of novel sulfated GM1b analogues as the mimics of Chol-1 (α-series) gangliosides : highly active ligands for neural siglecs"Carbohydr.Res.. 338. 1621-1639 (2003)

[Publications] Imamura, A.: "Di-tert-butylsilylene (DTBS) group-directed α-selective galactosylation unaffected by C-2 participating functionalities"Tetrahedron Lett.. 44. 6725-6728 (2003)

[Publications] Tsuchida, A.: "Synthesis of disialyl Lewis a (Le^a) structure in colon cancer cell lines by a sialyltransferase, ST6GalNAc VI, responsible for the synthesis of α-series ganglios"J.Biol.Chem.. 278. 22787-22794 (2003)

[Publications] Ando, H.: "Extending of the possibility of N-Troc-protected sialic acid donor toward variant sialo-glycoside synthesis"Tetrahedron Lett.. 44. 6883-6886 (2003)

[Publications] Hori, K.: "Synthetic study on Campylobacter jejuni lipopolysaccharides : an improved synthesis of a branched, heptose-containing trisaccharide core structure and its conversion into ganglioside GD3-related hexasaccharide"Eur.J.Org.Chem.. 3752-3760 (2003)

[Publications] Hara-Yokoyama, M.: "Novel sulfated gangliosides, high affinity ligands for neural siglecs, inhibit NADase activiy of leukocyte cell surface antigen CD38"Bioorg.Med.Chem.Lett.. 13. 3441-3445 (2003)

[Publications] Tamai, R: "Cell activation by monosaccharide lipid A analogues utilizingt Toll-like receptor 4"Immunology. 110. 66-72 (2003)

[Publications] Yamaguchi, M.: "Studies on the endogenous L-selectin ligands : Systematic and highly efficient total synthetic routes to lactamized-sialyl 6-O-sulfo Lewis x and other novel gangliosides containing lactamized neuraminic acid"Carbohydr.Res.. 338. 2793-2812 (2003)

[Publications] Ishihara, A.: "Synthesis and selectin-blocking activity of a novel analog of sulfatide : 3-C-carboxymethyl-galactosyl lipids"J.Carbohydr.Chem.. 22. 513-520 (2003)

[Publications] Fukunaga, K.: "Synthesis of lacto- and neolacto-series an ganglioside analogs containing N-glycolylneuraminic acid : probes for investigation of specific receptor structures recognized by influenza A viruses"J.Carbohydr.Chem.. 22. 919-937 (2003)

[Publications] Ando, H.: "Best Synthetic Methods : Carbohydrates"Elsevier. 430 (2003)

[Publications] 鈴木康夫: "コールドスプリングハーバー糖鎖生物学"丸善. 527 (2003)

木曽真岐阜大学, 農学部, 教授 (90092931)