Development of flavonoid probes and the binding mode of the target protein and quercetin derivatives
Development of flavonoid probes and the binding mode of the target protein and quercetin derivatives
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黄酮类探针的研制及目标蛋白与槲皮素衍生物的结合方式
DOI：
10.1016/j.bmc.2022.116854
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yamauchi Kosei
中科院分区：
文献类型：
--
作者：
Tsuchiya Ayaka;Kobayashi Miho;Kamatari Yuji O.;Mitsunaga Tohru;Yamauchi Kosei
本研究通过研究槲皮素衍生物靶蛋白的结合方式，探讨槲皮素衍生物抗癌细胞迁移活性的机制。新合成了5个类黄酮探针，用合成的类黄酮探针进行拉下实验，发现基质金属蛋白酶-1 （MMP-1）是槲皮素衍生物的靶蛋白。槲皮素和3- o -甲基槲皮素（3MQ）抑制MMP-1。SPR分析证实槲皮素衍生物与重组MMP-1催化结构域之间存在剂量依赖性相互作用。利用15n标记的MMP-1催化结构域进行1h - 15n异核单量子相干（HSQC）核磁共振分析表明，3MQ在MMP-1的金属离子周围相互作用。类黄酮探针的开发为发现新的靶蛋白和阐明类黄酮多种生物活性的核心机制提供了可能。
This study investigated the mechanism underlying anti-cancer cell migration activity of quercetin derivatives by investigating the binding mode of the target protein. Five flavonoid probes were newly synthesized, and pull down assay using synthesized flavonoid probes indicated matrix metalloproteinase-1 (MMP-1) as the target protein of quercetin derivatives. Quercetin and 3-O-methylquercetin (3MQ) inhibited MMP-1. SPR analysis demonstrated dose dependent interaction between quercetin derivatives and recombinant MMP-1 catalytic domain. And1H-15N heteronuclear single quantum coherence (HSQC) NMR analysis using15N-labeled MMP-1 catalytic domain indicated that 3MQ interacted around metal ions in the MMP-1. The development of flavonoid probes can broaden the possibility to discover the new target proteins and elucidate the core mechanisms of the multi bioactivity of flavonoids.