2003 年度実績報告書

乳酸菌表層への化学提示法を用いた経口ワクチンの開発

研究課題

研究課題/領域番号	15655059
研究機関	北海道大学
研究代表者	西村紳一郎北海道大学, 大学院・理学研究科, 教授 (00183898)
キーワード	バクテリア / 細胞壁 / ムラミン酸 / 表面プラズモン共鳴 / マンノース / 乳酸菌
研究概要	本年度は、まず、乳酸菌表面に導入したケトン基を足場として、糖鎖を乳酸菌表面に付加させることを検討した。糖鎖(マンノペンタオース)を、ケトン基と特異的に結合するオキシルアミノ基をもったリンカーをもちいて、乳酸菌表面に付加することに成功した。このことは、マンノースを特異的に認識するレクチンを固定化した基板に対する接着性の変化として、表面プラズモン共鳴法や蛍光顕微鏡観察により確認することができた。バクテリアの接着性は、有用細菌の腸内への常在化や、病原性細菌による感染などに関わっていることが知られており、本手法によって細菌の接着性能を変化させることができるということは大変重要な意味を持っている。次に、乳酸菌細胞壁への目的化合物の提示効率を上げることを検討した。人工の細胞壁前駆体を加えた培地でバクテリアを培養するときに、バクテリアの細胞壁前駆体の生合成を阻害する抗生物質(ホスホマイシン)を培養系に添加して天然の細胞壁前駆体の量を制限することにより、導入効率を挙げることに成功した。これらの成果は、Control of bacteria adhesion by cell-wall engineering R.Sadamoto, K.Niikura, T.Ueda, K.Monde, N.Fukuhara, S.-I.Nishimura J.Am.Chem.Soc., 2004, 126, in pressに掲載されることとなった。

研究成果

(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Sadamoto R.: "Control of bacteria adhesion by cell-wall engineering"J.Am.Chem.Soc.. 126(in press). (2004)
[文献書誌] Niikura K.: "Fluorescent Glyconanoparticles as a Sensitive Device to Monitor Sugar-Involving Molecular Events"Polymer J.. (in press). (2004)
[文献書誌] Tsukida T.: "Synthesis and Biological Activity of Selective Azasugar-Based TACE Inhibitors"Bioorg.Med.Chem.Lett.. (in press). (2004)
[文献書誌] Moriyama H.: "Azasugar-Based MMP/ADAM Inhibitors as Antipsoriatic Agent"J.Med.Chem.. (in press). (2004)
[文献書誌] Sato M.: "Site Specific Introduction of Sialic Acid to Insulin"Angew.Chem., Int.Ed.. (in press). (2004)
[文献書誌] Florence S.: "A practical synthesis of amphiphilic cyclodextrins fully sustituted with sugar on the upper face"Chem.Commun.. 2004. 596-597 (2004)
[文献書誌] Takegawa Y.: "Structural assignment of isomeric 2-aminopyridine derivatized oligosaccharides using MS^n spectral matching"Rapid Commun.Mass Spectrom.. 18. 385-391 (2004)
[文献書誌] Tachibana Y.: "Antifreeze Glycoproteins : Elucidation of the Structural Motifs That Are Essential for Antifreeze Activity"Angew.Chem., Int.Ed.. 7. 856-862 (2004)
[文献書誌] Andre S.: "Persubstituted cyclodextrin-based glycoclusters as inhibitors of protein-carbohydrate recognition using purified plant and mammalian lectins and wild-type and lectin-gene-transfected tumor cells as targets"Bioconjugate Chem.. 15. 87-98 (2004)
[文献書誌] Hoshi H.: "An engineered hyaluronan synthase : Characterization of recombinant human hyaluronan synthase 2 expressed in Escherichia coli"J.Biol.Chem.. 279. 2341-2349 (2004)
[文献書誌] Ohta T.: "Glycotentacles : Synthesis of cyclic glycopeptides toward a tailored blocker of influenza virus hemagglutinin"Angew.Chem., Int.Ed.. 42. 5186-5189 (2003)
[文献書誌] Moriyama H.: "Structure- Activity Relationships of Azasugar Based MMP/ADAM Inhibitors"Bioorg.Med.Chem.Lett. 13. 2737-2740 (2003)
[文献書誌] Moriyama H.: "Design, Synthesis and Evaluation of Novel Azasugar Based MMP/ADAM Inhibitors"Bioorg.Med.Chem.Lett. 13. 2741-2744 (2003)
[文献書誌] Monde K.: "Preparation of cruciferous phytoalexin related metabolites, (-)-dioxibrassinin and (-)-3-cyanomethyl-3-hydroxyoxindole, and determination of their absolute configurations by vibrational circular dichroism(VCD)"Tetrahedr Lett.. 44. 6017-6020 (2003)
[文献書誌] Furuike T.: "An efficient synthesis of a biantennary sialooligosaccharide analog using a 1,6-anhydro-β-lactose derivative as a key synthetic block"Tetrahedron. 59. 5105-5113 (2003)
[文献書誌] Nagahori N.: "Glycosyltransferase Microarray Displayed on the Glycolipid LB Membrane"Adv.Synth.Catal.. 345. 729-734 (2003)
[文献書誌] Matsuoka K.: "Synthesis of a useful anomeric thioacetate of an N-acetyllactosamine derivative and its application"Tetrahedr Lett.. 44. 3617-3620 (2003)
[文献書誌] Fukunaga K.: "Design, Synthesis, and Evaluation of β-Galactosylceramide Mimics Promoting β-Glucocerebrosidase Activity in Keratinocytes"Bioorg.Med.Chem.Lett.. 13. 813-815 (2003)

2003 年度 実績報告書

乳酸菌表層への化学提示法を用いた経口ワクチンの開発

研究代表者

西村 紳一郎 北海道大学, 大学院・理学研究科, 教授 (00183898)

研究成果

[文献書誌] Sadamoto R.: "Control of bacteria adhesion by cell-wall engineering"J.Am.Chem.Soc.. 126(in press). (2004)

[文献書誌] Niikura K.: "Fluorescent Glyconanoparticles as a Sensitive Device to Monitor Sugar-Involving Molecular Events"Polymer J.. (in press). (2004)

[文献書誌] Tsukida T.: "Synthesis and Biological Activity of Selective Azasugar-Based TACE Inhibitors"Bioorg.Med.Chem.Lett.. (in press). (2004)

[文献書誌] Moriyama H.: "Azasugar-Based MMP/ADAM Inhibitors as Antipsoriatic Agent"J.Med.Chem.. (in press). (2004)

[文献書誌] Sato M.: "Site Specific Introduction of Sialic Acid to Insulin"Angew.Chem., Int.Ed.. (in press). (2004)

[文献書誌] Florence S.: "A practical synthesis of amphiphilic cyclodextrins fully sustituted with sugar on the upper face"Chem.Commun.. 2004. 596-597 (2004)

[文献書誌] Takegawa Y.: "Structural assignment of isomeric 2-aminopyridine derivatized oligosaccharides using MS^n spectral matching"Rapid Commun.Mass Spectrom.. 18. 385-391 (2004)

[文献書誌] Tachibana Y.: "Antifreeze Glycoproteins : Elucidation of the Structural Motifs That Are Essential for Antifreeze Activity"Angew.Chem., Int.Ed.. 7. 856-862 (2004)

[文献書誌] Andre S.: "Persubstituted cyclodextrin-based glycoclusters as inhibitors of protein-carbohydrate recognition using purified plant and mammalian lectins and wild-type and lectin-gene-transfected tumor cells as targets"Bioconjugate Chem.. 15. 87-98 (2004)

[文献書誌] Hoshi H.: "An engineered hyaluronan synthase : Characterization of recombinant human hyaluronan synthase 2 expressed in Escherichia coli"J.Biol.Chem.. 279. 2341-2349 (2004)

[文献書誌] Ohta T.: "Glycotentacles : Synthesis of cyclic glycopeptides toward a tailored blocker of influenza virus hemagglutinin"Angew.Chem., Int.Ed.. 42. 5186-5189 (2003)

[文献書誌] Moriyama H.: "Structure- Activity Relationships of Azasugar Based MMP/ADAM Inhibitors"Bioorg.Med.Chem.Lett. 13. 2737-2740 (2003)

[文献書誌] Moriyama H.: "Design, Synthesis and Evaluation of Novel Azasugar Based MMP/ADAM Inhibitors"Bioorg.Med.Chem.Lett. 13. 2741-2744 (2003)

[文献書誌] Monde K.: "Preparation of cruciferous phytoalexin related metabolites, (-)-dioxibrassinin and (-)-3-cyanomethyl-3-hydroxyoxindole, and determination of their absolute configurations by vibrational circular dichroism(VCD)"Tetrahedr Lett.. 44. 6017-6020 (2003)

[文献書誌] Furuike T.: "An efficient synthesis of a biantennary sialooligosaccharide analog using a 1,6-anhydro-β-lactose derivative as a key synthetic block"Tetrahedron. 59. 5105-5113 (2003)

[文献書誌] Nagahori N.: "Glycosyltransferase Microarray Displayed on the Glycolipid LB Membrane"Adv.Synth.Catal.. 345. 729-734 (2003)

[文献書誌] Matsuoka K.: "Synthesis of a useful anomeric thioacetate of an N-acetyllactosamine derivative and its application"Tetrahedr Lett.. 44. 3617-3620 (2003)

[文献書誌] Fukunaga K.: "Design, Synthesis, and Evaluation of β-Galactosylceramide Mimics Promoting β-Glucocerebrosidase Activity in Keratinocytes"Bioorg.Med.Chem.Lett.. 13. 813-815 (2003)

2003 年度実績報告書

西村紳一郎北海道大学, 大学院・理学研究科, 教授 (00183898)