マクロサイクルハイブリッドペプチド/ポリケチド型の分子への化学酵素経路
Rahul M Kohli1, Martin D Burke, Junhua Tao
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Journal of the American Chemical Society
|June 12, 2003
まとめ
研究者は,多様なマクロサイクルハイブリッドペプチド-ポリケチドを合成するための化学酵素戦略を開発しました. この方法は,結合合成と酵素マクロサイクリングのための構成要素を使用し,新しい生物活性化合物の発見を可能にします.
科学分野:
- 自然製品のバイオシンセシス
- 薬用化学 薬用化学について
- 合成生物学 合成生物学とは
背景:
- ハイブリッドペプチドポリケチドは,医学的に,生物学的に重要な重要な天然製品です.
- 彼らの構造的複雑性と多様性は,複雑な生物合成経路から生じ,しばしば生物活性化のためのマクロサイクライゼーションが含まれます.
研究 の 目的:
- 多様なマクロサイクルハイブリッドペプチド-ポリケチドを合成するための効率的な化学酵素戦略を開発する.
- 薬剤発見のためのこれらの複雑な分子の組み合わせ図書館合成を可能にするために.
主な方法:
- 埋め込まれたポリケチド機能を持つ,Fmocで保護されたエプシロン-アミノ酸ビルディングブロックを使用しています.
- 溶性チオエステルまたは固体相結合として活性化された線形前駆体の組み合わせ合成を用いる.
- 非リボソームペプチド合成酵素から TycC TE触媒を用いたマクロサイクライゼーションが実証された.
主要な成果:
- マクロサイクライゼーションに適した多様な線形前駆物質の合成に成功しました.
- TycC TE触媒が様々な基板に対して持つ耐性を示した.
- 複雑なハイブリッドペプチド-ポリケチド構造にアクセスするための汎用プラットフォームを確立しました.
結論:
- 化学酵素戦略は,ステレオ化学的および機能的に多様なマクロサイクリックハイブリッド天然製品への効率的なアクセスを提供します.
- このアプローチは,新しい生物学的活動をスクリーニングするための複合図書館の生成を促進します.
- この方法は,改善された治療薬または全く新しい治療薬の発見に期待されます.
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