2003 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	15655059
Research Institution	Hokkaido University
Principal Investigator	西村紳一郎北海道大学, 大学院・理学研究科, 教授 (00183898)
Keywords	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
Research Abstract	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。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Sadamoto R.: "Control of bacteria adhesion by cell-wall engineering"J.Am.Chem.Soc.. 126(in press). (2004)
[Publications] Niikura K.: "Fluorescent Glyconanoparticles as a Sensitive Device to Monitor Sugar-Involving Molecular Events"Polymer J.. (in press). (2004)
[Publications] Tsukida T.: "Synthesis and Biological Activity of Selective Azasugar-Based TACE Inhibitors"Bioorg.Med.Chem.Lett.. (in press). (2004)
[Publications] Moriyama H.: "Azasugar-Based MMP/ADAM Inhibitors as Antipsoriatic Agent"J.Med.Chem.. (in press). (2004)
[Publications] Sato M.: "Site Specific Introduction of Sialic Acid to Insulin"Angew.Chem., Int.Ed.. (in press). (2004)
[Publications] Florence S.: "A practical synthesis of amphiphilic cyclodextrins fully sustituted with sugar on the upper face"Chem.Commun.. 2004. 596-597 (2004)
[Publications] Takegawa Y.: "Structural assignment of isomeric 2-aminopyridine derivatized oligosaccharides using MS^n spectral matching"Rapid Commun.Mass Spectrom.. 18. 385-391 (2004)
[Publications] Tachibana Y.: "Antifreeze Glycoproteins : Elucidation of the Structural Motifs That Are Essential for Antifreeze Activity"Angew.Chem., Int.Ed.. 7. 856-862 (2004)
[Publications] 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)
[Publications] Hoshi H.: "An engineered hyaluronan synthase : Characterization of recombinant human hyaluronan synthase 2 expressed in Escherichia coli"J.Biol.Chem.. 279. 2341-2349 (2004)
[Publications] Ohta T.: "Glycotentacles : Synthesis of cyclic glycopeptides toward a tailored blocker of influenza virus hemagglutinin"Angew.Chem., Int.Ed.. 42. 5186-5189 (2003)
[Publications] Moriyama H.: "Structure- Activity Relationships of Azasugar Based MMP/ADAM Inhibitors"Bioorg.Med.Chem.Lett. 13. 2737-2740 (2003)
[Publications] Moriyama H.: "Design, Synthesis and Evaluation of Novel Azasugar Based MMP/ADAM Inhibitors"Bioorg.Med.Chem.Lett. 13. 2741-2744 (2003)
[Publications] 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)
[Publications] 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)
[Publications] Nagahori N.: "Glycosyltransferase Microarray Displayed on the Glycolipid LB Membrane"Adv.Synth.Catal.. 345. 729-734 (2003)
[Publications] Matsuoka K.: "Synthesis of a useful anomeric thioacetate of an N-acetyllactosamine derivative and its application"Tetrahedr Lett.. 44. 3617-3620 (2003)
[Publications] 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 Fiscal Year Annual Research Report

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

Principal Investigator

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

Research Products

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

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

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

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

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

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

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

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

[Publications] 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)

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

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

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

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

[Publications] 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)

[Publications] 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)

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

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

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

西村紳一郎北海道大学, 大学院・理学研究科, 教授 (00183898)