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抗菌活性強化のための非正規的,ダイナミックな共性単環および多環ペプチドマクロサイクルに対する汎用的なアプローチ
James F Reuther1, Andrew C Goodrich2, P Rogelio Escamilla1
1Department of Chemistry , University of Texas at Austin , Austin , Texas 78712 , United States.
Journal of the American Chemical Society
|February 22, 2018
まとめ
研究者は,強化された抗菌剤のための複雑なペプチドマクロサイクル (MCs) を作成する新しい方法を開発しました. この技術は,単一,二重,三重のループを形成することによって,既存の抗菌ペプチドの有効性を改善します.
科学分野:
- 生物化学
- 薬剤化学
- 材料科学
背景:
- ペプチドオリゴマーは,その生物互換性および調節性のために,抗菌剤のための有望な支架です.
- 複数のループを持つ複雑なペプチドマクロサイクル (MC) の形成は,治療開発における重要な課題である.
研究 の 目的:
- シングル,ダブル,トリプルループペプチドマクロサイクル (MCs) の作成のための多用途な方法を開発する.
- これらの新しいマクロサイクル構造を用いてペプチドの抗菌性能を高める.
主な方法:
- ディアルデヒドまたはディヒドラジドクロスリンクヤーによるダイナミックな水素濃縮を用いた.
- 合成ペプチドは,アルデヒドを含むサイドチェーンで,ヒドラジドC末端樹脂で,樹脂組立のために.
- MALDI-TOF MS,HPLC,およびSDS-PAGEを用いてマクロサイクル形成が確認された.
主要な成果:
- シングル,ダブル,トリプルループのペプチドMCを成功裏に形成した.
- 樹脂割れで直接調節可能なペプチドMCアセンブリが得られる.
- マクロサイクルの構造に組み込まれると,ブフォリンIIの抗菌性能の有意な強化が示された.
結論:
- ダイナミック・コバルント化学は,複雑なペプチドマクロサイクルを構成するための多用途なアプローチを提供します.
- 水素濃縮によるペプチドマクロサイクリングは,線形配列と比較して,抗菌効果を大幅に高めます.
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