真の3D多様化可能な化学空間を持つ配列可能なタンパク質模倣ペプチド図書館の構築
Zhonghan Li1, Shiqun Shao1, Xiaodong Ren1
1Department of Chemistry , University of California, Riverside , Riverside , California 92521 , United States.
Journal of the American Chemical Society
|October 27, 2018
まとめ
タンパク質を模倣する新しい バイサイクルペプチドを開発しました 1つのペプチドはc- Mycオンコタンパク質を標的にし,転写を妨害することで癌細胞の増殖を抑制する.
科学分野:
- 薬剤化学
- 分子生物学
- バイオテクノロジー
背景:
- c-Mycのような内在的に乱れたタンパク質は 挑戦的な治療目標です
- タンパク質模倣薬は 伝統的な薬の代替品として 有望です
研究 の 目的:
- 多様な化学空間を持つ新しいバイサイクリックペプチドのライブラリを作成します
- c-Mycの活性を抑制するペプチドを特定し特徴づけること
主な方法:
- クリック化学とリングクロージングメタテシスを用いたバイサイクルペプチドの合成.
- 線形化後のエドマン分解と質量スペクトロメトリによるペプチド配列決定.
- c-Myc E363-R378 エピトープに対する高通量スクリーニング
- グリオブラストーマ細胞系におけるペプチドの有効性のインビトロ試験.
主要な成果:
- 空間的に多様なサイドチェーンのナノサイズの硬いバイサイクルペプチドのライブラリが合成されました.
- c- Mycオンコタンパク質に結合する特定のペプチドが特定されました.
- このペプチドは細胞内伝達を示し,c- Myc媒介による転写を妨害し,膠芽細胞増殖を抑制した.
結論:
- サイクリックペプチドは新しい治療法を開発する際の 汎用的な基盤です
- c- Mycを特定のペプチド阻害剤で標的化すると,膠原細胞腫の治療の可能性が示される.
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