Ugiのような生物合成経路が,ボンベシン受容体サブタイプ3アゴニストをコードする
Joonseok Oh1,2, Nam Y Kim1,2, Haiwei Chen3
1Department of Chemistry , Yale University , New Haven , Connecticut 06520 , United States.
Journal of the American Chemical Society
|September 21, 2019
まとめ
研究者達は,免疫抑制剤であるラブドプリンから自発的に生成される新しいオピン・グリコペプチドを発見した. これらの化合物は,ボンベシン受容体サブタイプ-3 (BB3) Gタンパク質結合受容体 (GPCR) を活性化します.
科学分野:
- 自然製品化学
- 微生物の生化学
- 薬理学について
背景:
- アイソシアニドの機能群は多くの天然製品に存在します.
- Xenorhabdus と Photorhabdus のバクテリアの免疫抑制剤であるラブドゥシンは,イソシアン酸群を含み,毒性に関連しています.
- ラブドシンの生物合成経路と自然な機能は完全に理解されていません.
研究 の 目的:
- ラブドシンの新種の天然産物を特徴づける
- これらの新しい化合物の生物合成メカニズムを解明する.
- 新しく発見された天然製品の 薬理学的活性を調べる
主な方法:
- バクテリア培養から分離された天然製品の化学的特徴.
- 遺伝子操作 (遺伝子クラスター削除) を用いた生物合成経路の調査.
- Gタンパク質結合受容体 (GPCR) の活性を決定する生化学的測定法
主要な成果:
- 新しいオピン・グリコペプチドのクラスであるラボドプラニンの識別と特徴付け.
- ラブドプラニンの自発的生成が"ウギのような"反応によって示される.
- Rhabdoplaninsは,ボンベシン受容体サブタイプ-3 (BB3) GPCRの強力なアゴニストとして特定されました.
結論:
- ラボドプラニンは 独特の生物合成起源を持つ 新しい種類の天然製品です
- この多成分反応経路は 自然産物の生物合成において前例のないものです
- ラボドプラニンは,BB3 GPCR経路を標的とした治療薬として潜在性を示しています.
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