2,2'-Bipyridine ligandoside: a novel building block for modifying DNA with intra-duplex metal complexes.
2,2'-Bipyridine ligandoside: a novel building block for modifying DNA with intra-duplex metal complexes.
复制标题
DOI：
10.1021/ja005785n
复制
发表时间：
2001-04
影响因子：
15
通讯作者：
Haim Weizman and;Y. Tor
中科院分区：
文献类型：
--
作者：
Haim Weizman and;Y. Tor
DNA双螺旋的结构、动力学和识别特性继续吸引着化学家。虽然已经设计了巧妙和多样的方法来探测DNA的各种表面（例如，凹槽粘合剂，金属复合物），但在探索螺旋内部方面做得很少。该部分暴露的域由堆叠的杂环组成，其将H-键供体和受体投射到内部以及两个不同的凹槽中。这种芳香π堆叠介导电荷转移过程的能力最近已经成为中心阶段2，并促使我们考虑对DNA核心进行修饰。[3]我们设想将带电的金属络合物放置在DNA螺旋的中心，如图1所示。4，5核苷模拟物，在此被称为配体苷，其中杂环碱基被强螯合剂取代，是我们方法的关键（图1）。6、7配体糖苷应满足以下要求：（a）与标准DNA合成相容;（B）对金属离子的亲和力高于杂环碱基;（c）形成与DNA碱基对尺寸相当的复合物。2，2′-联吡啶因其高稳定性和对多种金属离子的亲和性而被选为配体。8，9建模揭示了bpy与糖的直接连接导致金属络合时双链体的压缩。因此，在配体的5位和2′-脱氧-D-核糖之间引入了一个亚甲基。饱和的亚甲基桥使配体糖苷松弛，并导致复合物在DNA双链体内更好地拟合。
The structure, dynamics, and recognition properties of the DNA double helix continue to fascinate chemists. While ingenious and diverse approaches have been devised to probe the various surfaces of DNA (eg, groove binders, metal complexes), 1 little has been done to explore the interior of the helix. This partially exposed domain is comprised of stacked heterocycles that project H-bond donors and acceptors into the interior as well as the two distinct grooves. The ability of this aromatic π-stack to mediate charge-transfer processes has recently taken center stage2 and prompted us to consider modification to the DNA core. 3 We have envisioned the placement of charged metal complexes at the center of the DNA helix as illustrated in Figure 1. 4, 5 Nucleoside mimics, hereby coined ligandosides, where the heterocyclic base is replaced by a strong chelator, are key to our approach (Figure 1). 6, 7 A ligandoside should meet the following requirements:(a) Be compatible with standard DNA synthesis;(b) have higher affinity for metal ions than the heterocyclic bases;(c) form complexes with comparable dimensions to a DNA base pair. 2, 2′-Bipyridine has been selected as the ligand due to its high stability and affinity to numerous metal ions. 8, 9 Modeling reveals that direct attachment of the bpy to the sugar results in compression of the duplex upon metal complexation. A methylene group has therefore been introduced between position 5 of the ligand and the 2′-deoxy-D-ribose. The saturated methylene bridge relaxes the ligandoside and results in better fitting of the complex within the DNA duplex.