Role of stacking interactions in the binding sequence preferences of DNA bis-intercalators: insight from thermodynamic integration free energy simulations.
Role of stacking interactions in the binding sequence preferences of DNA bis-intercalators: insight from thermodynamic integration free energy simulations.
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DOI：
10.1093/nar/gki916
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发表时间：
2005
影响因子：
14.9
通讯作者：
Gago F
中科院分区：
文献类型：
--
作者：
Marco E;Negri A;Luque FJ;Gago F
天然喹喔啉双嵌入剂棘霉素和曲骨菌素A或喹啉棘霉素衍生物2 QN所表现出的优先结合DNA上CpG结合位点的主要结构决定因素是鸟嘌呤（G）的2-氨基。然而，通过在DNA分子中引入2-氨基腺嘌呤（= 2，6-二氨基嘌呤，D）碱基代替腺嘌呤（A）来重新定位该基团，已显示导致结合位点的急剧重新分布，以及2 QN与序列DTDT的超紧密结合。此外，脱甲基化的曲骨素类似物TANDEM和CysMeTANDEM以高亲和力结合天然DNA中的TpA步骤，与CpI步骤的结合不那么紧密，尽管腺苷和含次黄嘌呤的核苷肌苷（I）在小沟中提供相同的氢键结合可能性。为了研究2 QN相对于GCGC位点对DTDT的结合亲和力的增加以及与ATAT相比CysMeTANDEM和ICIC之间的结合能的显著损失，已经进行了一系列涉及DNA碱基对之间转换的热力学积分自由能模拟。我们的研究结果表明，这些化合物的杂芳环之间的堆叠相互作用的静电分量和构成嵌入位点的碱起着非常重要的作用，在调制其结合亲和力。
The major structural determinant of the preference to bind to CpG binding sites on DNA exhibited by the natural quinoxaline bis-intercalators echinomycin and triostin A, or the quinoline echinomycin derivative, 2QN, is the 2-amino group of guanine (G). However, relocation of this group by means of introduction into the DNA molecule of the 2-aminoadenine (=2,6-diaminopurine, D) base in place of adenine (A) has been shown to lead to a drastic redistribution of binding sites, together with ultratight binding of 2QN to the sequence DTDT. Also, the demethylated triostin analogs, TANDEM and CysMeTANDEM, which bind with high affinity to TpA steps in natural DNA, bind much less tightly to CpI steps, despite the fact that both adenosine and the hypoxanthine-containing nucleoside, inosine (I), provide the same hydrogen bonding possibilities in the minor groove. To study both the increased binding affinity of 2QN for DTDT relative to GCGC sites and the remarkable loss of binding energy between CysMeTANDEM and ICIC compared with ATAT, a series of thermodynamic integration free energy simulations involving conversions between DNA base pairs have been performed. Our results demonstrate that the electrostatic component of the stacking interactions between the heteroaromatic rings of these compounds and the bases that make up the intercalation sites plays a very important role in the modulation of their binding affinities.
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影响因子：
2.9
作者：
ADDESS, KJ;FEIGON, J
通讯作者：
FEIGON, J
影响因子：
14.9
作者：
ADDESS, KJ;FEIGON, J
通讯作者：
FEIGON, J
DOI：
10.1107/s090744490500137x
发表时间：
2005-04-01
影响因子：
2.2
作者：
Cuesta-Seijo, JA;Sheldrick, GM
通讯作者：
Sheldrick, GM
影响因子：
2.9
作者：
ADDESS, KJ;FEIGON, J
通讯作者：
FEIGON, J
DOI：
10.1016/0006-291x(72)90243-4
发表时间：
1972-01-01
影响因子：
3.1
作者：
ARNOTT, S;HUKINS, DWL
通讯作者：
HUKINS, DWL