Cell-membrane coated iron oxide nanoparticles for isolation and specific identification of drug leads from complex matrices
Cell-membrane coated iron oxide nanoparticles for isolation and specific identification of drug leads from complex matrices
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DOI：
10.1039/c9nr01292c
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发表时间：
2019-04-07
期刊：
影响因子：
6.7
通讯作者：
Ciesla, Lukasz M.
中科院分区：
文献类型：
--
作者：
Sherwood, Jennifer;Sowell, Josiah;Ciesla, Lukasz M.
缺乏合适的工具来从复杂基质中识别潜在的药物先导是药物发现的瓶颈。在这里，我们报告了一种新的方法来筛选复杂的矩阵靶向跨膜受体的新的药物引线。使用（34）烟碱受体作为模型系统，我们成功地证明了这种新工具从复杂混合物中特异性识别和有效提取结合化合物的能力。通过透射电子显微镜证实了细胞膜包覆的纳米颗粒的形成。特别是，我们已经开发了一种直接的工具来评估细胞膜上的功能性（34）烟碱受体的存在。通过配体钓鱼实验检查与（34）烟碱受体的特异性配体结合，并通过高效液相色谱-二极管阵列检测器和电喷雾电离质谱法进行确认。该工具具有巨大的潜力，可以改变药物发现过程，重点是识别靶向跨膜蛋白的化合物，因为超过50%的现代药物使用膜蛋白作为主要靶标。
The lack of suitable tools for the identification of potential drug leads from complex matrices is a bottleneck in drug discovery. Here, we report a novel method to screen complex matrices for new drug leads targeting transmembrane receptors. Using (34) nicotinic receptors as a model system, we successfully demonstrated the ability of this new tool for the specific identification and effective extraction of binding compounds from complex mixtures. The formation of cell-membrane coated nanoparticles was confirmed by transmission electron microscopy. In particular, we have developed a direct tool to evaluate the presence of functional (34) nicotinic receptors on the cell membrane. The specific ligand binding to (34) nicotinic receptors was examined through ligand fishing experiments and confirmed by high-performance liquid chromatography coupled with diode-array detection and electrospray ionization mass spectrometry. This tool has a great potential to transform the drug discovery process focusing on identification of compounds targeting transmembrane proteins, as more than 50% of all modern pharmaceuticals use membrane proteins as prime targets.