Anisotropy studies of tRNA-T box antiterminator RNA complex in the presence of 1,4-disubstituted 1,2,3-triazoles.
Anisotropy studies of tRNA-T box antiterminator RNA complex in the presence of 1,4-disubstituted 1,2,3-triazoles.
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1,4-二取代 1,2,3-三唑存在下 tRNA-T 盒抗终止子 RNA 复合物的各向异性研究。
DOI：
10.1016/j.bmcl.2011.09.095
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发表时间：
2011
影响因子：
2.7
通讯作者：
Hines,JV
中科院分区：
文献类型：
--
作者：
Zhou,S;Acquaah-Harrison,G;Bergmeier,SC;Hines,JV
在许多革兰氏阳性细菌中，tRNA与T盒抗菌素RNA元件的结合是T盒核糖开关机制的关键组成部分，该机制调节了必需基因。采用基于荧光各向异性的方法筛选了一系列1,4-二取代1,2,3-三唑，以破坏tRNA-T盒抗菌剂RNA的相互作用。一些化合物将各向异性降低了50%以上，这可能表明在结合抗菌素RNA方面存在显著竞争。总体结构-活性趋势表明，N-1和C-4上的取代基都可能参与配体结合。此外，配合物的各向异性不仅被可能与RNA发生静电相互作用的配体显著降低，而且还被可能发生π -π堆叠或其他疏水相互作用的配体显著降低，这表明这些非静电相互作用可能被用于未来开发靶向和破坏这种具有重要医学意义的核蛋白开关功能的化合物。
The binding of tRNA to the T box antiterminator RNA element is a critical component of the T box riboswitch mechanism that regulates essential genes in many Gram-positive bacteria. A series of 1,4-disubstituted 1,2,3-triazoles was screened for disruption of the tRNA-T box antiterminator RNA interaction using a fluorescence anisotropy-based assay. Several compounds reduced the anisotropy greater than 50% likely indicating significant competition for binding antiterminator RNA. General structure–activity trends indicated that the substituents at both N-1 and C-4 likely are involved in ligand binding. In addition, the anisotropy of the complex was significantly decreased not only by ligands with the possibility for electrostatic interactions with the RNA, but also by ligands with the potential for π–π stacking or other hydrophobic interactions indicating that these non-electrostatic interactions could possibly be utilized in the future development of compounds that target and disrupt the function of this medicinally important riboswitch.