キュルビット[6]ウリル・プロモテッド・クリック・ケミストリー・フォー・プロテイン・モディフィケーション

Joel A Finbloom¹, Kenneth Han¹, Clancy C Slack^1,2

¹Department of Chemistry, University of California , Berkeley, California 94720, United States.

Journal of the American Chemical Society

|June 27, 2017

まとめ

クキュルビチューリル (CB6) の超分子化学を用いた新しいクリック化学法を開発しましたこの多用途な技術により,高度な生体材料のための多様な生体結合物質の合成が可能になります.

科学分野:

超分子化学
化学生物学
バイオコンジュガーション

背景:

アジド・アルキン・サイクロアディションはバイオコンジュガート合成の重要な反応であり,銅 (I) またはストレイン・プロモートされた変種が広く使用されている.
キュルビット[6]ウリル (CB6) 誘発のサイクル添加はロタキサン合成に限られており,複雑なバイオコンジュガートには適用されていません.

研究の目的:

CB6誘導によるアジドアルキンのサイクロアディションを汎用的な生物結合技術に適応させる.
最適化CB6クリック化学を用いて新種のタンパク質を合成する.

主な方法:

交互反応性機能群を欠いた新しいCB6クリック化学基板を開発した.
CB6-促進されたアジド-アルキンサイクル添加のための最適化反応条件.
タンパク質-ペプチド,タンパク質-DNA,タンパク質-ポリマー,およびタンパク質-薬物を含む様々なタンパク質結合体を合成した.

主要な成果:

ロタキサン合成から生物結合に成功しました.
複雑なタンパク質の結合物が高効率で合成された.
CB6 クリックは,配列生物結合のためのストレンス促進アジド-アルキンサイクロアディションと相容性を示した.

結論:

CB6が誘発したクリック化学はタンパク質の生物結合の新しく強力な方法を提供します
この技術は様々な用途のための複雑な生体材料の作成を容易にする.
CB6 クリック・ケミストリーは,高度なバイオコンジュガート合成のためのツールキットを拡張します.

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