Accelerated assembly of G-quadruplex structures by a small molecule
Accelerated assembly of G-quadruplex structures by a small molecule
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DOI：
10.1021/bi9905922
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发表时间：
1999-06-01
期刊：
影响因子：
2.9
通讯作者：
Hurley, LH
中科院分区：
文献类型：
--
作者：
Han, HY;Cliff, CL;Hurley, LH
在碱金属阳离子（尤其是钾和钠）存在的情况下，具有两个富含 G 重复序列的 DNA 寡聚物会结合成四聚体平行 G-四链体或各种二聚体反平行 G-四链体。这种结构的形成通常是一个非常缓慢的过程。一些蛋白质，例如尖毛虫端粒结合蛋白的β亚基，以类似分子伴侣的方式促进G-四链体结构的形成。在本报告中，我们提供了有关苝衍生物 PIPER 在 G 四链体结构组装中的作用的数据，作为小配体在多核苷酸二级结构组装中充当驱动程序的第一个例子。凝胶迁移实验表明，PIPER 可以显着加速含有两个串联重复的人类端粒序列 (TTAGGG) 的 DNA 寡聚物与二聚体和四聚体 G 四链体的缔合。在此过程中，PIPER 将低聚物二聚动力学从二级改为一级。 10 μM PIPER 的存在加速了各种二聚体 G-四链体的组装，估计是 2 μM 寡聚体的 100 倍。这些结果意味着 G-四链体相互作用剂引起的一些生物效应，例如后期桥的诱导，可能源于此类化合物组装 G-四链体的倾向。
In the presence of alkali cations, notably potassium and sodium, DNA oligomers that possess two G-rich repeats associate into either a tetrameric parallel G-quadruplex or a variety of dimeric antiparallel G-quadruplexes. The formation of such structures is normally a very slow process. Some proteins, such as the beta-subunit of the Oxytricha telomere-binding protein, promote the formation of G-quadruplex structures in a chaperone-like manner. In this report, we present data concerning the role of a perylene derivative, PIPER, in the assembly of G-quadruplex structures as the first example of a small ligand behaving as a driver in the assembly of polynucleotide secondary structures. Gel-shift experiments demonstrate that PIPER can dramatically accelerate the association of a DNA oligomer containing two tandem repeats of the human telomeric sequence (TTAGGG) into di- and tetrameric G-quadruplexes. In so doing, PIPER alters the oligomer dimerization kinetics from second to first order. The presence of 10 mu M PIPER accelerates the assembly of varied dimeric G-quadruplexes an estimated 100-fold from 2 mu M oligomer, These results imply that some biological effects elicited by G-quadruplex-interactive agents, such as the induction of anaphase bridges, may stem from the propensity such compounds have for assembling G-quadruplexes.