2025-07-11 京都大学
スタキベンザールAは、ASNSの556番目のリジン残基(K556)を介した共有結合阻害剤である。
<関連情報>
- https://www.kyoto-u.ac.jp/ja/research-news/2025-07-11-0
- https://www.kyoto-u.ac.jp/sites/default/files/2025-07/web_2507_Kakeya-ab84ab728be5702c321c18d3c802102d.pdf
- https://pubs.acs.org/doi/10.1021/acs.jnatprod.5c00572
共有結合性アスパラギン合成酵素阻害剤としての天然リジン活性メロテルペノイド、スタキベンザルA-C Natural Lysine-Reactive Meroterpenoids, Stachybenzals A–C, as Covalent Asparagine Synthetase Inhibitors
Lei Zhang,Yanjun Pan,Hidehiro Uekusa,Takehiro Suzuki,Naoshi Dohmae,Akira Hattori,Yoshinori Hirano,and Hideaki Kakeya
Journal of Natural Products Published: July 9, 2025
DOI:https://doi.org/10.1021/acs.jnatprod.5c00572
Abstract
Asparagine synthetase (ASNS) is a promising molecular target for cancer chemotherapy. We previously reported bisabosqual A (Bis A), a natural covalent ASNS inhibitor that binds to K556 of ASNS. In this study, to discover other natural covalent ASNS inhibitors, we used a Lys derivative (N-Boc-l-Lys) to target Lys-reactive metabolites in crude extract of the fungus Stachybotrys ruwenzoriensis RF-6853. We discovered three new meroterpenoids possessing an o-phthalaldehyde moiety, stachybenzals A–C (1–3), with ASNS inhibitory activity.
