裂け目-[2]ロタキサンの細胞内輸送機構の決定

Xiaofeng Bao¹, Idit Isaacsohn, Angela F Drew

¹Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221, USA.

Journal of the American Chemical Society

|September 14, 2006

まとめ

ロタキサンは,機械的分子機械であり,細胞の物質輸送を促進します. 形状の柔軟性,特にホイールの滑り動きは,治療薬の効率的なトランスメブラン伝達に不可欠です.

科学分野:

超分子化学超分子化学
ナノテクノロジーナノテクノロジー
細胞生物学細胞生物学

背景:

ロタキサンは,スイッチやセンサーとしての潜在的な応用を持つ相互接続された分子構造である.
最近の発見は,細胞内物質輸送のエージェントとしてのロタキサンの有用性を強調しています.
ロタキサン媒介によるトランスメブラン輸送のメカニズムは明らかにする必要があります.

研究の目的:

ロータキサン媒介型トランスメブラン輸送のメカニズムを調査する.
ゲスト・バインディングとセルラー・デリバリーにおけるコンフォーマーション・フレキシビリティの役割を決定する.
標的型薬物投与におけるロタキサンの治療の可能性を評価する.

主な方法:

ロタキサン構造を分析するための二次元NMRスペクトロスコーピー.
形状的にロックされたロタキサンを生成するための化学的改変.
様々な溶媒 (水性,DMSO,クロロフォーム) でのゲスト結合親和性研究.
光ペプチドとフローサイトメトリを用いた細胞吸収研究.
輸送メカニズムを調査するために,温度とATP依存度測定を行います.

主要な成果:

裂け目を含むロタキサンは"閉じた"および"開いた"形状に存在する.
適合性の柔軟性により,水溶液およびDMSO溶液におけるゲスト結合が強化されます.
ロックされたロタキサンでは,柔軟なロタキサンと比較してペプチド輸送効率が低下しています.
ロタキサン濃度に応じて,ペプチドの高い細胞吸収 (89-98%) が達成されました.
輸送は主に温度とATPに依存せず,受動的な膜通過を示唆しています.

結論:

ロタキサンホイールの滑り動きは,細胞物質の配送に不可欠です.
ロタキサンは,ゲストの結合と細胞の吸収を高めるための機械的装置として機能します.
ロタキサンは,治療薬を細胞に投与するナノデバイスの有望な新しいクラスを表しています.

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