Studies of antimicrobial oligosaccharides

• Project/Area Number: 15K07857
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Nagoya Institute of Technology
• Principal Investigator: Yamamura Hatsuo 名古屋工業大学, 工学(系)研究科(研究院), 教授 (80220440)
• Co-Investigator(Renkei-kenkyūsha): MIYAGAWA Atsushi 名古屋工業大学, 大学院工学研究科, 助教 (60469921)
• Project Period (FY): 2015-10-21 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 抗菌 / 抗生物質 / シクロデキストリン / クリック反応 / 抗菌剤 / 耐性菌 / オリゴ糖

Outline of Final Research Achievements

Novel antibiotics have been highly demanded because of emergence of drug-resistant bacteria. Here we investigated membrane-active antimicrobial oligosaccharide cyclodextrins. These possess functional groups to permeabilize bacterial cell membranes. The polyfunctionalization of sugars was achieved through a microwave-assisted click reaction. A survey using the derivatives with systematically varied functionalities clarified the unique correlation of the antimicrobial activity of these compounds with their structures. The dependence of number of functional groups in the molecule demonstrates that the assembly of the groups is necessary for expressing antimicrobial activity. The compounds having selective toxicity against bacteria including multidrug-resistant pathogens were observed. The results demonstrate that the sugar is a versatile molecular scaffold for rationally designed structures and can be used for the development of new antibiotics.

Research Products

• [Journal Article] Antimicrobial Poly(Amino-Modified Alkyl) β-Cyclodextrins Synthesized via Click Reaction (2018)
  • Author(s): Hatsuo Yamamura, Miho Nonaka, Shingo Okuno, Ryogo Mitsuhashi, Hisato Kato, Takashi Katsu, Kazufumi Masuda, Koichi Tanimoto, Haruyoshi Tomita, Atsushi Miyagawa
  • Journal Title: MedChemComm Volume: 9 Issue: 3 Pages: 509-518
  • DOI: 10.1039/c7md00592j
  • Peer Reviewed / Open Access
• [Journal Article] Syntheses and structure-membrane active antimicrobial activity relationship of alkylamino-modified glucose, maltooligosaccharide, and amylose (2017)
  • Author(s): Hatsuo Yamamura, Takahiro Mabuchi, Tomoki Ishida, Atsushi Miyagawa
  • Journal Title: Chemical Biology and Drug Design Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 細菌膜傷害性オリゴ糖の開発研究 (2018)
  • Author(s): 山村初雄、谷本弘一、富田治芳
  • Organizer: 第92回日本感染症学会学術講演会 第66回日本化学療法学会総会 合同学会
• [Presentation] 細菌膜傷害による抗菌性シクロデキストリン誘導体のクリック反応による合成、構造および活性の相関 (2017)
  • Author(s): 山村 初雄 石田 智基 野中 美帆 宮川 淳
  • Organizer: 日本化学会第９７春季年会
  • Place of Presentation: 横浜
  • Year and Date: 2017-03-16
• [Presentation] 抗菌オリゴ糖およびアミロースのクリック反応による合成と構造―活性相関 (2017)
  • Author(s): 山村初雄、馬渕貴浩、石田智基、林勇磨、宮川淳
  • Organizer: 第３３回シクロデキストリンシンポジウム
• [Presentation] アルキルアミノ基を導入した抗菌α及びβ-シクロデキストリン (2016)
  • Author(s): 野中美帆、石田智基、宮川淳、山村初雄
  • Organizer: 第３３回シクロデキストリンシンポジウム
  • Place of Presentation: 高松
  • Year and Date: 2016-09-08
• [Presentation] アルキルアミノ基を導入した抗菌γ-シクロデキストリン誘導体 (2016)
  • Author(s): 萩原達也、林勇磨、野中美帆、石田智基、宮川淳、山村初雄
  • Organizer: 第３３回シクロデキストリンシンポジウム
  • Place of Presentation: 高松
  • Year and Date: 2016-09-08