2001 Fiscal Year Annual Research Report

複合糖質を素材とした糖鎖分子と生体分子の相互作用の解明

Research Project

Project/Area Number	12672062
Research Institution	Kyoritsu College of Pharmacy
Principal Investigator	竹田忠紘共立薬科大学, 薬学部, 教授 (90106253)
Keywords	Anti-ulcer-pectic polysaccharide / Bupleurum falcatum / Chemical synthesis / Glycosphingolipid / Parasite / Amphoteric glycosphingolipid / Pheretime hilgendorfi / β-mannosidic linkage
Research Abstract	近年、植物、動物をとわず細胞の認識に係わる現象に様々な形で、細胞表層の糖鎖が関与することが示唆されている。複合糖質の糖鎖の担う生物機能を解明するため、その素材を1)漢薬サイコ中に含有される抗潰瘍活性を有する酸性多糖体、2)無脊椎動物中に含有される糖脂質に求めた。抗潰瘍活性を有する酸性多糖体は、分子量63,000を有し、rhamnogalacturonan core(PG-1)にβ-(1-3)galactanが結合し、更にその側鎖にglucuronic acid又は4-O-methyl glucuronic acidが結合した6結合のgalactose鎖を有している。これらオリゴ糖鎖及び、繰り返し構造を有するオリゴ糖誘導体を合成し、さらに、bupleuran2IIcに対する抗体(抗bupleurann2IIc/PG-1抗体)が作成され、そのエピトープとしてPG-1の側鎖部分であるGlcA1-6Gal,4-O-Me-GlcA1-6Gal, GlcA1-6Gall-6Gal,4-O-Me-GlcA1-6Gall-6Ga1が関連していると思われ、これらエピトープ部分の二糖又は三糖誘導体を含むモデル化合物の合成を試み、柴胡由来ペクチン様多糖のモデル化合物としてepitope糖鎖の糖クラスターへと導いた。寄生動物エキノコックス、及びマンソン裂頭条虫より見いだされたフコース含有新規糖脂質はhost-parasite interactionの観点から機能上興味があり、動物生薬として用いられている「地龍」及び「水蛭」由来の糖脂質Manα1→4Galβ1→6Galβ1-ceramide及びGalα1→6(Manα1→4)Galβ1→6Galβ1-ceramide、さらには同動物より見いだされたガラクトースの6位にホスフォコリン基が結合した両性イオン型糖脂質の合成を行い、ヒスタミン遊離抑制などの生物活性について検討した。

Research Products

(10 results)

All Other

All Publications (10 results)

[Publications] Noriyasu Hada: "Syntheses of model compounds related to an antigenic epitope in pectic polysaccharides from B.falcatum"Carbohydrate Research. 334. 7-17 (2001)
[Publications] Noriyasu Hada: "Synthetic studies on 4 glycosphingolipids from P.phyla"Chem.Pharm.Bull.. 49. 1464-1467 (2001)
[Publications] Iso Ohtuska: "Synthetic studies on glycosphingolipids from P.phyla Synthesis of amphoteric glycolipid analogues"Chem.Pharm.Bull.. 50(in press). (2002)
[Publications] Sonoda Y, Yamamoto D, Kasahara T et al.: "FTY720, a novel immunosuppressive agent, induces apoptosis in human glioma cells"Blochom Blophys Res Commun. 281(2). 282-288 (2001)
[Publications] Funakoshi M, Tago K, Kasahara T et al.: "A MEK inhibitor, PD98059 enhances IL-1-induced NF-kB activation by the enhanced and sustained degradation of lkBα"Blochom Blophys Res Commun. 283(2). 248-253 (2001)
[Publications] Mori M, Terui Y, Kasahara T et al.: "Antitumor effect of b2-microglobulin in leukemic cell-bearing mice via apoptosis-inducing activity : activation of caspase-3 and NF-kB"Cancer Res.. 61(11). 4414-4417 (2001)
[Publications] Kasahara T, Matsushima K.: "Macrophage signaling, apoptosis, lectins and leukocyte trafficking"Trends Immunol.. 22(11). 593-594 (2001)
[Publications] Tago K, Funakoshi M, Kasahara T et al.: "Presence of a genistein-responsive inhibitory mechanism on interleukini 1a-induced NE-kB activation"Eur J Blochem.. 268(24). 6526-6533 (2001)
[Publications] Matsui S, Matsumoto S, Adachi R, Kasahara T et al.: "LIM kinase 1 modulates opsonized zymosan-triggered activation of macrophage-like U937 cells. Possible involvement of phospho"J Bilo Chem.. 277(1). 544-549 (2002)
[Publications] Kasahara T, Koguchi E, Funakoshi M, et al.: "Anti-apoptotic action of focal adhesion kinase (FAK) against the ionizing radiation"Antloxldant Redox Signaiing. (in press). (2002)

2001 Fiscal Year Annual Research Report

複合糖質を素材とした糖鎖分子と生体分子の相互作用の解明

Principal Investigator

竹田 忠紘 共立薬科大学, 薬学部, 教授 (90106253)

Research Products

[Publications] Noriyasu Hada: "Syntheses of model compounds related to an antigenic epitope in pectic polysaccharides from B.falcatum"Carbohydrate Research. 334. 7-17 (2001)

[Publications] Noriyasu Hada: "Synthetic studies on 4 glycosphingolipids from P.phyla"Chem.Pharm.Bull.. 49. 1464-1467 (2001)

[Publications] Iso Ohtuska: "Synthetic studies on glycosphingolipids from P.phyla Synthesis of amphoteric glycolipid analogues"Chem.Pharm.Bull.. 50(in press). (2002)

[Publications] Sonoda Y, Yamamoto D, Kasahara T et al.: "FTY720, a novel immunosuppressive agent, induces apoptosis in human glioma cells"Blochom Blophys Res Commun. 281(2). 282-288 (2001)

[Publications] Funakoshi M, Tago K, Kasahara T et al.: "A MEK inhibitor, PD98059 enhances IL-1-induced NF-kB activation by the enhanced and sustained degradation of lkBα"Blochom Blophys Res Commun. 283(2). 248-253 (2001)

[Publications] Mori M, Terui Y, Kasahara T et al.: "Antitumor effect of b2-microglobulin in leukemic cell-bearing mice via apoptosis-inducing activity : activation of caspase-3 and NF-kB"Cancer Res.. 61(11). 4414-4417 (2001)

[Publications] Kasahara T, Matsushima K.: "Macrophage signaling, apoptosis, lectins and leukocyte trafficking"Trends Immunol.. 22(11). 593-594 (2001)

[Publications] Tago K, Funakoshi M, Kasahara T et al.: "Presence of a genistein-responsive inhibitory mechanism on interleukini 1a-induced NE-kB activation"Eur J Blochem.. 268(24). 6526-6533 (2001)

[Publications] Matsui S, Matsumoto S, Adachi R, Kasahara T et al.: "LIM kinase 1 modulates opsonized zymosan-triggered activation of macrophage-like U937 cells. Possible involvement of phospho"J Bilo Chem.. 277(1). 544-549 (2002)

[Publications] Kasahara T, Koguchi E, Funakoshi M, et al.: "Anti-apoptotic action of focal adhesion kinase (FAK) against the ionizing radiation"Antloxldant Redox Signaiing. (in press). (2002)

竹田忠紘共立薬科大学, 薬学部, 教授 (90106253)