Real-Time Monitoring of Ligand Binding to G-Quadruplex and Duplex DNA by Whispering Gallery Mode Sensing
Real-Time Monitoring of Ligand Binding to G-Quadruplex and Duplex DNA by Whispering Gallery Mode Sensing
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DOI：
10.1021/acssensors.6b00301
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发表时间：
2016-09
期刊：
影响因子：
8.9
通讯作者：
Sirirat Panich;M. Sleiman;Isobel Steer;S. Ladame;J. Edel
中科院分区：
文献类型：
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作者：
Sirirat Panich;M. Sleiman;Isobel Steer;S. Ladame;J. Edel
靶向G-四链体的小分子的治疗潜力已经获得了可信度，因为这种结构被证明是在人类细胞中形成的，并在人类基因组中非常普遍，最明显的是在端粒末端和癌基因启动子中。在这里，我们执行耳廊模式(WGM)传感来监测DNA与小分子的相互作用。与大多数现有技术不同，WGM传感具有许多优点，包括高灵敏度、实时分析、易于获取动力学参数，以及比目前的黄金标准低得多的成本。在这项工作中，评估了五个已知的DNA结合配体与固定在球形微谐振器上的G-四链或双链DNA的相互作用。共振模从四链(或双链)配体结合的诱导位移被用来估计动力学参数。测定了这五种配体的缔合和解离速率常数(分别为kon和koff)和解离平衡常数(Kd)。
The therapeutic potential of small molecules targeting G-quadruplexes has gained credibility since such structures were shown to form in human cells and to be highly prevalent in the human genome, most notably at telomere ends and in oncogene promoters. Herein, we perform whispering gallery mode (WGM) sensing for monitoring DNA–small molecule interactions. Unlike most existing technologies, WGM sensing offers numerous advantages including high sensitivity, real-time analysis, easy access to kinetic parameters, and much lower cost than current gold standards. In this work, interactions of five known DNA-binding ligands with either G-quadruplex or duplex DNA immobilized on a sphere microresonator have been assessed. The induced shift of the resonant mode from quadruplex (or duplex)–ligand binding was used to estimate kinetic parameters. Association and dissociation rate constants (kon and koff, respectively) as well as dissociation equilibrium constants (KD) were measured for these five ligands binding to b...