A general method for discovering inhibitors of protein-DNA interactions using photonic crystal biosensors.
A general method for discovering inhibitors of protein-DNA interactions using photonic crystal biosensors.
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DOI：
10.1021/cb800057j
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发表时间：
2008-07-18
影响因子：
4
通讯作者：
Cunningham, Brian T.
中科院分区：
文献类型：
--
作者：
Chan, Leo L.;Pineda, Maria;Heeres, James T.;Hergenrother, Paul J.;Cunningham, Brian T.
蛋白质-DNA相互作用对于基本细胞过程如转录、DNA损伤修复和凋亡是必不可少的。因此，这些相互作用的小分子干扰物可能是研究这些生物过程的有力工具，并且这些化合物将具有作为治疗剂的巨大潜力。不幸的是，有几种方法可用于快速鉴定破坏蛋白质-DNA相互作用的化合物。在这里，我们表明，光子晶体（PC）技术可用于检测蛋白质-DNA相互作用，并可用于高通量筛选模式，以确定化合物，防止蛋白质-DNA结合。PC技术用于检测DNA序列依赖性（细菌毒素-抗毒素系统MazEF）和DNA序列非依赖性（人凋亡诱导因子（AIF））蛋白质-DNA相互作用之间的结合。进一步利用PC技术筛选AIF-DNA相互作用的抑制剂，并通过该筛选确定金精三羧酸为AIF的第一个体外抑制剂。光子晶体方法的一般性和简单性应使该技术能够在鉴定抑制蛋白质-DNA结合的化合物方面找到广泛的用途。
Protein–DNA interactions are essential for fundamental cellular processes such as transcription, DNA damage repair, and apoptosis. As such, small molecule disruptors of these interactions could be powerful tools for investigation of these biological processes, and such compounds would have great potential as therapeutics. Unfortunately, there are few methods available for the rapid identification of compounds that disrupt protein–DNA interactions. Here we show that photonic crystal (PC) technology can be utilized to detect protein–DNA interactions, and can be used in a high-throughput screening mode to identify compounds that prevent protein–DNA binding. The PC technology is used to detect binding between protein–DNA interactions that are DNA-sequence-dependent (the bacterial toxin–antitoxin system MazEF) and those that are DNA-sequence-independent (the human apoptosis inducing factor (AIF)). The PC technology was further utilized in a screen for inhibitors of the AIF–DNA interaction, and through this screen aurin tricarboxylic acid was identified as the first in vitro inhibitor of AIF. The generality and simplicity of the photonic crystal method should enable this technology to find broad utility for identification of compounds that inhibit protein–DNA binding.
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