Proteome interrogation using gold nanoprobes to identify targets of arctigenin in fish parasites
Proteome interrogation using gold nanoprobes to identify targets of arctigenin in fish parasites
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使用金纳米探针进行蛋白质组分析来识别鱼类寄生虫中牛蒡甙元的靶标
DOI：
10.1186/s12951-020-00591-9
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发表时间：
2020-02
影响因子：
10.2
通讯作者：
Wang Gaoxue
中科院分区：
文献类型：
--
作者：
Tu Xiao;Tan Xiaoping;Qi Xiaozhou;Huang Aiguo;Ling Fei;Wang Gaoxue
金纳米粒子是应用最广泛的纳米材料之一。特别是其独特的化学和物理性质使其成为药物靶点鉴定的有希望的候选者，但其在寄生虫中的应用尚不清楚。本文以GNPs为基础，对天然生物活性化合物artigenin （ARG）抗鱼单系寄生虫小林egyrodactylus kobayashi的药物靶点进行了鉴定。在鉴定目标之前，表面带有ARG的GNPs显示出进入活体寄生虫甚至细胞核或线粒体的能力，这使得结合的化合物能够直接与寄生虫任何位置的目标蛋白接触。同时，经化学修饰的化合物仍能保持对g虫的驱虫功效。kobayashii。以上结果均为GNPs用于药物靶标结合特异性的可靠性提供了保证。随后，通过对寄生虫裂解物细胞蛋白质组的分析，确定了myosin-2和UNC-89是ARG inG潜在的直接靶蛋白。kobayashii。此外，RNA-seq转录组学和iTRAQ蛋白质组学结果表明，ARG浴处理后，肌球蛋白-2的表达在转录和蛋白水平上均下调，而UNC-89的表达仅在mRNA水平上下调。Myosin-2是蠕虫被皮中表达的重要结构肌肉蛋白，将其作为我们的靶点将有助于进一步优化抑制剂，以促进未来药物的发现。此外，我们的研究结果表明，GNPs可以很容易地应用于其他未知靶点的寄生虫药物，从而促进在任何病原体或疾病模型中更广泛的治疗药物设计。
Gold nanoparticles (GNPs) are one of the most widely used nanomaterials in various fields. Especially, the unique chemical and physical properties make them as the promising candidates in drug target identification, unfortunately, little is known about their application in parasites. In this paper, GNPs were employed as new solid support to identify drug targets of natural bioactive compound arctigenin (ARG) against fish monogenean parasiteGyrodactylus kobayashi. Before target identification, GNPs with ARG on the surface showed the ability to enter the live parasites even the nucleus or mitochondria, which made the bound compounds capable of contacting directly with target proteins located anywhere of the parasites. At the same time, chemically modified compound remained the anthelminthic efficacy againstG. kobayashii. The above results both provide assurance on the reliability of using GNPs for drug target-binding specificity. Subsequently, by interrogating the cellular proteome in parasite lysate, myosin-2 and UNC-89 were identified as the potential direct target proteins of ARG inG. kobayashii. Moreover, results of RNA-seq transcriptomics and iTRAQ proteomics indicated that myosin-2 expressions were down-regulated after ARG bath treatment both in transcript and protein levels, but for UNC-89, only in mRNA level. Myosin-2 is an important structural muscle protein expressed in helminth tegument and its identification as our target will enable further inhibitor optimization towards future drug discovery. Furthermore, our findings demonstrate the power of GNPs to be readily applied to other parasite drugs of unknown targets, facilitating more broadly therapeutic drug design in any pathogen or disease model.
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影响因子：
5.8
作者：
Tong, Mark Y.;Cassa, Christopher A.;Kohane, Isaac S.
通讯作者：
Kohane, Isaac S.
影响因子：
5.3
作者：
通讯作者：
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影响因子：
5.6
作者：
Qadota, Hiroshi;Blangy, Anne;Xiong, Ge;Benian, Guy M.
通讯作者：
Benian, Guy M.
具有肽-Au缀合物的自组装热敏发光纳米颗粒用于细胞成像和药物输送
影响因子：
9.1
作者：
Zhang Xiaoyuan;Liu Wei;Wang Haixia;Zhao Xinne;Zhang Zhenfang;Nienhaus Gerd Ulrich;Shang Li;Su Zhiqiang
通讯作者：
Su Zhiqiang
DOI：
10.3390/nano1010031
发表时间：
2011-06-14
期刊：
Nanomaterials (Basel, Switzerland)
影响因子：
--
作者：
Tiwari PM;Vig K;Dennis VA;Singh SR
通讯作者：
Singh SR