自然産物とその生合成起源を特定するための反応性カルボニルの標的化
Tucker Maxson1, Jonathan I Tietz1, Graham A Hudson1
1Department of Chemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Journal of the American Chemical Society
|November 1, 2016
まとめ
研究者は新しい同位体標識法を開発し,新しい天然製品 (NP) を発見しました. このアプローチは従来の方法の限界を克服し デイミノ・アンチペインのような 未知の化合物の特定を可能にします
科学分野:
- 化学生物学
- 自然 産物 の 発見
- メタボロミクス
背景:
- 伝統的な天然製品 (NP) の発見は,化合物の豊富さと高い再発見率によって制限されるバイオアッセイ主導の方法に依存しています.
- 薬剤開発と化学生物学ツールのための新しいNPの発見を強化するために,直交的な方法が必要です.
研究 の 目的:
- 反応性に基づくNPスクリーニングのアイソトープタグベースの拡張を開発する.
- アルデヒドとケトンを含むNPを検出するための新しいアミノキシを含む探査機を作成します.
- アルデヒドを含むプロテアース阻害剤の遺伝的基礎を特定する.
主な方法:
- NPsの化学選択的ラベル付けのための二ブロミン化アミノキシプローブを開発した.
- バクテリア抽出物の反応性ベースのスクリーニングで探査機を利用した.
- バイオインフォマティック分析と異質発現を用いて,生物合成遺伝子クラスタを特定した.
主要な成果:
- バクテリアの抽出物で 痛みを和らげる新薬デイミノ・アンチペインを 発見しました
- デイミノ・アンチペインの生成を担当する生物合成遺伝子のクラスタを決定した.
- アルデヒドを含むペプチドプロテアース阻害剤の遺伝的基礎を明らかにした.
結論:
- イソトープタグベースの反応性スクリーニング方法は,新しいNPの発見を効果的に促進します.
- このアプローチは,重要なプロテアゼ阻害体の生物合成に関する新しい洞察を提供します.
- 開発された方法は,天然製品発見のレパートリーを拡大するための強力なツールを提供します.
さらに関連する動画
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The carbonyl center is activated by...
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01:23Protecting Groups for Aldehydes and Ketones: Introduction
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01:15Oxidations of Aldehydes and Ketones to Carboxylic Acids
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Aldehydes readily undergo oxidation in strong oxidizing agents such as potassium permanganate and chromic acid. The oxidation can also be carried out using mild oxidizing agents such as silver oxide. In fact, aldehydes can be easily oxidized...
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01:18Nucleophilic Addition to the Carbonyl Group: General Mechanism
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02:23Alcohols from Carbonyl Compounds: Reduction
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Catalytic hydrogenation is similar to the reduction of an alkene or alkyne by adding H2 across the pi bond in the presence of transition metal catalysts like Raney Ni, Pd–C, Pt, or Ru. Aldehydes and ketones can be reduced by this method, often under mild to moderate heat (25–100°C) and...
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