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

• Project/Area Number: 15655059
• Research Category: Grant-in-Aid for Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Chemistry related to living body
• 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)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: バクテリア / 細胞壁 / ムラミン酸 / 乳酸菌 / フッ素 / 抗菌剤 / 表面プラズモン共鳴 / マンノース

Research Abstract

バクテリア細胞壁へのムラミン酸誘導体導入による表面修飾という本手法の発展として、ムラミン酸誘導体をもちいた新しい抗菌剤について検討した。
ムラミン酸の4位をフッ素化した細胞壁前駆体誘導体(フッ素化パークヌクレオチド)を、N-アセチルガラクトサミンを出発原料として合成するルートを新たに確立した。このフッ素化パークヌクレオチドは、バクテリア細胞壁合成経路においてLipidIIの合成を阻害することにより、抗菌作用を示すことが期待される。この抗菌作用について乳酸菌を用いて調べた。菌株には、ラクトバシルス属のL.plantarum JCM1149を用いた。この細菌をフッ素化パークヌクレオチドを1mg/ml(0.87mMの,0.01mg/ml(0.0087mM)で含む培地(市販のラクトバチリMRSブロスを22.5g/lで蒸留水に溶かしたもの)に添加し、嫌気性条件下37℃で培養した。比較として、化合物(Ia)を含まない培地でも培養した。1、2、3、5、7、10時間後の細菌の個体数を、寒天培地上で形成されたコロニーを数えることにより算出した。各時間での細菌の個体数を算出した結果、フッ素化パークヌクレオチドを含む培地では含まない培地にくらべ、増殖率が低下することが確認された。これらの成果はOrg.Lett.2004,6,1753-1756に掲載された。

Research Products

• [Journal Article] Synthesis of 4-fluorinated UDP-MurNAc pentapeptide as an inhibitor of bacterial growth (2004)
  • Author(s): Ueda T
  • Journal Title: Org.Lett. 6 Pages: 1753-1756
• [Journal Article] Chemo-enzymatic synthesis of fluorinated 2-N-acetamidosugar nucleotides using UDP-GlcNAc pyrophosphorylase (2004)
  • Author(s): Feng F
  • Journal Title: Org.Biomol.Chem 2 Pages: 1617-1623
• [Journal Article] Control of bacteria adhesion by cell-wall engineering (2004)
  • Author(s): Sadamoto R
  • Journal Title: J.Am.Chem.Soc. 126 Pages: 3755-3761
• [Patent(Industrial Property Rights)] バクテリアの効率的表面修飾方法 (2004)
  • Inventor(s): 西村 紳一郎 他3名
  • Industrial Property Rights Holder: 西村 紳一郎
  • Industrial Property Number: 2004-101518
  • Filing Date: 2004-03-30
• [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)