Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, PR China.
Int J Biol Macromol. 2013 Jan;52:1-8. doi: 10.1016/j.ijbiomac.2012.08.015. Epub 2012 Aug 24.
Compounds that bind and stabilize selectively human telomeric quadruplex DNA structures are of significant interest due to their potential to inhibit telomerase and to halt tumor cell proliferation. In our previous study, we found that three novel phenanthroline derivatives could induce and stabilize significantly the formation of an antiparallel structure of human telomeric G-quadruplex DNA (G(3)(T(2)AG(3))(3)), moreover, these compounds could bind selectively to G-quadruplex over duplex. In order to understand their binding nature, in this work we investigated the interactions of compounds 1-3 with human telomeric G-quadruplex and i-motif (C(3)(A(2)TC(3))(3)) DNAs together with calf thymus DNAs (ct DNA) by means of absorption, fluorescence and CD spectroscopies and competition dialysis assay. Results showed that all three compounds showed the highest affinity for G-quadruplex structure although with least affinity for ct DNA. Compounds 1-3 could also stabilize the structure of i-motif with an increase in melting temperature (ΔT(m)) of 7.6, 7.2 and 10.1°C, respectively, in the presence of 10 times excess of compounds. Their binding stoichiometric ratios were 2:1 and 1:1 for G-quadruplex and i-motif DNAs, respectively. The thermodynamic parameters results indicated that the binding of compound to either quadruplex or duplex DNAs was entropically driven and hydrophobic force played a major role in the reaction.
由于能够抑制端粒酶并阻止肿瘤细胞增殖，因此能够选择性结合和稳定人端粒四链体 DNA 结构的化合物具有重要意义。在我们之前的研究中，我们发现三种新型菲咯啉衍生物可以显著诱导和稳定人端粒 G-四链体 DNA（G(3)(T(2)AG(3))(3)）的反平行结构形成，此外，这些化合物可以选择性地结合 G-四链体而不是双链体。为了了解它们的结合性质，在这项工作中，我们通过吸收、荧光和 CD 光谱以及竞争透析实验研究了化合物 1-3 与人类端粒 G-四链体和 i- 基序（C(3)(A(2)TC(3))(3)）DNA 以及小牛胸腺 DNA（ct DNA）的相互作用。结果表明，尽管与 ct DNA 的亲和力最小，但所有三种化合物都表现出与 G-四链体结构的最高亲和力。化合物 1-3 还可以稳定 i- 基序的结构，在存在 10 倍过量化合物的情况下，其熔解温度（ΔT(m)）分别增加了 7.6、7.2 和 10.1°C。它们与 G-四链体和 i- 基序 DNA 的结合计量比分别为 2:1 和 1:1。热力学参数结果表明，化合物与任何四链体或双链体 DNA 的结合都是熵驱动的，疏水作用力在反应中起主要作用。
