バクテリアのトランスグリコシラーゼ阻害剤の親和性ベースのスクリーニング
Wei-Shen Wu1,2, Wei-Chieh Cheng2, Ting-Jen R Cheng2
1Graduate Institute of Life Sciences, National Defense Medical Center , 161 Minquan E. Road, Section 6, Neihu, Taipei 114, Taiwan.
Journal of the American Chemical Society
|February 8, 2018
まとめ
研究者は細菌のトランスグリコシラーゼを標的とした 新種の抗生物質を見つけるための新しい方法を開発しました このスクリーンは,抗菌性細菌に対して有効なベナスタチン派生体およびアルボファンギンを含む強力な抗菌化合物を特定しました.
科学分野:
- 薬剤化学
- 微生物学
- 薬物の発見
背景:
- 抗生物質耐性は 世界的な危機であり 新種の抗菌剤の開発が 求められています
- 耐性細菌感染と闘うための新しい抗生物質が 緊急に必要とされています
研究 の 目的:
- 新しい抗生物質を特定するための親和性ベースのリガンドスクリーニング方法を開発する.
- 細菌の表面トランスグリコシラゼ酵素を標的にする
- 強力な抗菌物質を 複合的な天然産物から分離する
主な方法:
- ペニシリン結合タンパク質は,親和性に基づくスクリーニングのためにビーズに固定されます.
- 化合物の識別と特徴づけのために,質量スペクトロメトリーを使用した.
- モエノミシンAとサリチラニリド類を基準阻害剤として比較試験を行った.
主要な成果:
- ベナスタチン誘導体 (11-13) とアルボフンギン (14) の4つの強力な抗菌化合物を成功裏に分離した.
- 化合物11と14は,グラム陽性およびグラム陰性細菌に対する幅広い有効性を示した.
- これらの化合物は,薬剤耐性菌株を含む,Acinetobacter baumannii,Clostridium difficile,Staphylococcus aureusを含む,挑戦的な病原体に対して,微小からナノモールの最小抑制濃度で有効でした.
結論:
- 開発された親和性に基づくスクリーニング方法は,新しい抗生物質の発見に有効です.
- ベナスタチン誘導体とアルボファンギンは新しい抗生物質の開発に有望な候補である.
- これらの化合物は,多剤耐性細菌によって引き起こされる感染症の治療に重要な可能性を示しています.
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