水中の化学選択性アミノニトリル結合によるペプチド結合
Pierre Canavelli1, Saidul Islam1, Matthew W Powner2
1Department of Chemistry, University College London, London, UK.
Nature
|July 12, 2019
まとめ
研究者らは,水中のアルファペプチドを生成するための新しい方法を開発しました. このアルファ-アミノニトリル結合は選択的で,すべての20のタンパク質原性アミノ酸を許容し,生命の初期進化の洞察を提供します.
科学分野:
- 生物化学
- 生命 研究 の 起源
- 合成化学
背景:
- アミド結合の形成は化学と生物学において重要であるが,水中のアルファペプチド結合の方法は限られている.
- 生命の進化はペプチドと硫黄に依存した反応が RNAベースのタンパク質合成に先行したことを示唆しています
- 初期のペプチド合成の鍵となるアミノアシルチオエステル形成の強力なメカニズムはまだ実証されていない.
研究 の 目的:
- 水中のアルファペプチド結合のための新しい化学的方法を開発する.
- ペプチド合成に 適した分子を利用する
- タンパク質生成アミノ酸を 容認できる結合法を作る
主な方法:
- 化学選択性アルファアミノニトリル結合反応を発症した.
- 硫化水素,チオアセテート,フェルシアン化物またはシアノアセチレンを使用した.
- ペプチド結合におけるアルファ-アミノニトリル反応性,pKa,およびN-アシレーションの役割を調査した.
主要な成果:
- 水中のアルファペプチドの形成に成功した.
- アルファ-アミノニトリル結合の選択性が実証された.
- すべての20のタンパク質生成アミノ酸残留に対する耐性を示した.
- 製品安定化と前駆体活性化における重要な要因としてN-アシレーションを特定した.
結論:
- 開発されたアルファ-アミノニトリル結合は,アルファ-ペプチドを合成するための堅牢で水に適合する方法である.
- この方法は,チオエステル依存ペプチド結合がRNA依存タンパク質合成に先行したという仮説を支持する.
- 短いN-アシルペプチドナトリルは,化学進化の初期に妥当な基板として提案されている.
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