2003 Fiscal Year Annual Research Report

生理活性糖鎖の構造的基盤と高次生命機能の制御

Research Project

Project/Area Number	15631009
Research Institution	Gifu University
Principal Investigator	木曽真岐阜大学, 農学部, 教授 (90092931)
Co-Investigator(Kenkyū-buntansha)	梶原康宏横浜市立大学, 理学部, 助教授 (50275020) 橋本康弘理研フロンティア, 糖鎖機能部門, プロジェクトリーダー(研究職) (80164797) 石田秀治岐阜大学, 農学部, 助教授 (20203002) 平竹潤京都大学, 化学研究所, 助教授 (80199075) 垣内隆京都大学, 工学部, 教授 (20135552)
Keywords	ノイラミン酸 / シアリルルイスX / ガングリオシド / シグレック / シアロ糖鎖 / 白血球表面抗原 / セレクチン
Research Abstract	(1)シアリル6-O-スルホルイスXを起点とするL-セレクチン依存性の新しい免疫制御機構の構造的基盤を解明するために、ラクタム化ノイラミン酸を含むガングリオシドGM4、硫酸化シアリルパラグロボシド、及び硫酸化/非硫酸化シアリルルイスXの系統的合成を行った。すなわち、ノイラミン酸の高効率的一段階ラクタム化は、デ-N-アセチルシアル酸(ノイラミン酸)を含むガングリオシドをあらかじめ合成し、DMF中65℃でHBTU/HOBtと反応させることにより高収率にて達成された。これらの人工ガングリオシドを用いて、(a)ラクタム化ノイラミン酸残基とGlcNAcの6-O-硫酸基の両者がG159抗体により認識されていること、(b)L-フコースはG159抗体による認識に本質的な寄与をしていないことを明らかにした(Carbohydr.Res.,333,2793,2003)。 (2)シアル酸認識レクチン「シグレック」の糖鎖認識特異性を解明するためにα-(2-3)/α-(2-6)-ジシアリルラクトテトラオシルセラミドの合成を行い(Carbohydr.Res.,338,501,2003)、シアロ糖鎖の構造的基盤に基づく「シグレック-7」の高次認識機構について調査した。X-線結晶構造解析により、α-(2-3)/α-(2-6)-ジシアリルラクトテトラオースが2つのシアル酸を介してクロスリンクすることを明らかにした(未発表)。 (3)ガングリオシドGT1bが有する分子内部のタンデムシアル酸は、2つの硫酸基によって代替され、白血球表面抗原CD38のNADase活性を強力に阻害することを発見した(Bioorg.Med.Chem.Lett.,13,3441,2003)。

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 end 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 a-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 gangliosides"J.Biol.Chem.. 278. 22787-22794 (2003)
[Publications] Ando H.: "Extending of the possibility of N-Troc-protected sialic acid donor toward varient sialoglycoside 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 activity of leukocyte cell surface antigen CD38"Bioorg.Med.Chem.Lett.. 13. 3441-3445 (2003)
[Publications] Tamai, R.: "Cell activation by monosaccharide lipid A analogues utilizing 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 ganglioside analogs containing N-glycolylne uraminic 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

生理活性糖鎖の構造的基盤と高次生命機能の制御

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 end 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 a-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 gangliosides"J.Biol.Chem.. 278. 22787-22794 (2003)

[Publications] Ando H.: "Extending of the possibility of N-Troc-protected sialic acid donor toward varient sialoglycoside 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 activity of leukocyte cell surface antigen CD38"Bioorg.Med.Chem.Lett.. 13. 3441-3445 (2003)

[Publications] Tamai, R.: "Cell activation by monosaccharide lipid A analogues utilizing 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 ganglioside analogs containing N-glycolylne uraminic 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)