UMR176 CNRS, Institut Curie, Centre de Recherche, Centre Universitaire, 91405 Orsay, France.
Chemistry. 2010 Jan 18;16(3):878-89. doi: 10.1002/chem.200901989.
A collection of 15 homodimeric and 5 heterodimeric macrocyclic bisintercalators was prepared by one- or two-step condensation of aromatic dialdehydes with aliphatic diamines; notably, the heterodimeric scaffolds were synthesized for the first time. The binding of these macrocycles to DNA duplexes containing a mispaired thymine residue (TX), as well as to the fully paired control (TA), was investigated by thermal denaturation and fluorescent-intercalator-displacement experiments. The bisnaphthalene derivatives, in particular, the 2,7-disubstituted ones, have the highest selectivity for the TX mismatches, as these macrocycles show no apparent binding to the fully paired DNA. By contrast, other macrocyclic ligands, as well as seven conventional DNA binders, show lesser or no selectivity for the mismatch sites. The study demonstrates that the topology of the ligands plays a crucial role in determining the mismatch-binding affinity and selectivity of the macrocyclic bisintercalators.
合成了 15 个同二聚体和 5 个异二聚体的大环双嵌入剂，通过芳香二醛与脂肪二胺的一步或两步缩合得到；值得注意的是，异二聚体支架是首次合成的。通过热变性和荧光嵌入剂置换实验研究了这些大环化合物与含有错配胸腺嘧啶残基（TX）的 DNA 双链体以及完全配对的对照（TA）的结合。双萘衍生物，特别是 2,7-取代的那些，对 TX 错配具有最高的选择性，因为这些大环化合物与完全配对的 DNA 没有明显的结合。相比之下，其他大环配体以及七种常规 DNA 结合剂对错配位点的选择性较小或没有。该研究表明，配体的拓扑结构在确定大环双嵌入剂的错配结合亲和力和选择性方面起着至关重要的作用。
