Goulaouic H, Carteau S, Subra F, Mouscadet J F, Auclair C, Sun J S
Laboratoire de Pharmacologie Moléculaire, CNRS URA 147, INSERM U 140, Institut Gustave Roussy, Villejuif, France.
Biochemistry. 1994 Feb 15;33(6):1412-8. doi: 10.1021/bi00172a018.
In order to further characterize the binding of the hybrid molecule NetOPC [bis(pyrrolecarboxamide)-oxazolopyridocarbazole conjugate] to double-stranded DNA, we have performed a molecular modeling study to investigate the binding modes of the complexes possibly formed between NetOPC and synthetic polynucleotides poly [(dA-dT)]2, poly [(dA).d(T)], and poly [d(G-C)]2 and interpreted the results in the light of the experimentally determined binding parameters. In agreement with experimental data, the modeling study suggests that whatever was the binding mode of the complex formed, the complexation energy is markedly lower (thus favorable) for AT-containing polynucleotides than for poly d[(G-C)]2. With both poly [d(A).d(T)] and poly [d(A-T)]2, the most energetically favored complex has netropsin and OPC moieties bound simultaneously in the minor groove of DNA. The second favored complex exhibits the bimodal binding, i.e., intercalation of OPC and minor groove binding of the netropsin moiety. For both types of complex, the energy of complex formation is slightly lower with poly [d(A).d(T)]. The binding site sizes of the modeled complexes are about seven and four base pairs to the full groove and bimodal binding, respectively.
为了进一步表征杂合分子NetOPC[双（吡咯甲酰胺）-恶唑并吡啶咔唑共轭物]与双链DNA的结合情况，我们进行了一项分子建模研究，以探究NetOPC与合成多核苷酸聚[（dA-dT）]2、聚[（dA）·d（T）]和聚[d（G-C）]2可能形成的复合物的结合模式，并根据实验测定的结合参数对结果进行解释。与实验数据一致，建模研究表明，无论形成的复合物的结合模式如何，含AT的多核苷酸的络合能都比聚d[（G-C）]2明显更低（因此更有利）。对于聚[（dA）·d（T）]和聚[（dA-T）]2，能量上最有利的复合物是放线菌素和OPC部分同时结合在DNA的小沟中。第二个有利的复合物表现出双峰结合，即OPC的嵌入和放线菌素部分的小沟结合。对于这两种类型的复合物，聚[（dA）·d（T）]形成复合物的能量略低。建模复合物的结合位点大小对于全沟结合和双峰结合分别约为七个和四个碱基对。
