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Click chemistry approach to characterize curcumin-protein interactions in vitro and in vivo

机译:点击化学方法在体外和体内表征姜黄素 - 蛋白质相互作用

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Curcumin, a bis-alpha,beta-unsaturated beta-diketon dietary compound from turmeric, is among the most promising dietary compounds for preventing chronic diseases. Previous research has shown that curcumin is highly reactive toward protein thiols to form curcumin-protein adducts, however, the interactions of curcumin with proteins are under-studied. Here we report the design and synthesis of "click" chemistry probes of curcumin, mono-propargyl curcumin (mono-Cur) and di-propargyl curcumin (di-Cur), and use the click probes to study curcumin-proteins interactions in vitro and in vivo. We find that compared with di-Cur, the mono-Cur probe has more potent biological effects and enhanced effects to label proteins in cultured cells, suggesting that mono-Cur is a better click probe to study the biological actions of curcumin. Furthermore, using the mono-Cur probe, we find that oral administration of this probe in mice leads to formation of curcumin-protein adducts in colon and liver tissues of C57BL/6 mice, suggesting that curcumin could covalently modify cellular proteins in vivo. Together, these results could help us to better understand protein-curcumin interactions. These results could in part explain the poor pharmacokinetics of curcumin; in addition, formation of these protein adducts could contribute to the health-promoting effects of curcumin. (C) 2019 Elsevier Inc. All rights reserved.
机译:来自姜黄的姜黄素,双-α,β-不饱和的β-二氧酮饮食化合物是用于预防慢性疾病的最有前途的饮食化合物。以前的研究表明,姜黄素对蛋白质硫醇具有高反应性以形成姜黄素 - 蛋白质加合物,然而,姜黄素与蛋白质的相互作用进行了研究。在这里,我们报告了“点击”化学探针的设计和合成的姜黄素,单丙基戊二酮(单丙基)和二 - 丙基姜黄素(Di-Cur),并使用点击探针在体外研究姜黄素 - 蛋白相互作用体内。我们发现与Di-Cy相比,单次CUR探针对培养细胞中的标记蛋白质具有更有效的生物学效果和增强的效果,表明单次CUR是更好的点击探针以研究姜黄素的生物学作用。此外,使用单次CUR探针,我们发现小鼠中该探针的口服给药导致C57BL / 6小鼠的结肠癌和肝组织中的姜黄素 - 蛋白质加合物,表明姜黄素可以共价修饰体内细胞蛋白。这些结果可以帮助我们更好地了解蛋白质姜黄素相互作用。这些结果可以分为解释姜黄素的差的药代动力学;此外,这些蛋白质加合物的形成可能有助于姜黄素的健康促进作用。 (c)2019 Elsevier Inc.保留所有权利。

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