McCarthy S L, Hinde R J, Miller K J, Anderson J S, Basch H, Krauss M
Department of Chemistry, Rensselaer Polytechnic Institute, Troy, New York 12181.
Biopolymers. 1990 Mar-Apr;29(4-5):785-90. doi: 10.1002/bip.360290412.
The results of a study of the binding to DNA of substituted cis-Pt(II) diammines, (cis-DP) are presented. Computer modeling of a series of cis-Pt(NH2R)2(+2)--where R = H, CH3, cyclopropyl, cyclobutyl, and cyclopentyl--to N7(G) atoms of two adjacent intrastrand guanine bases in a square planar complex in a pentamer duplex of DNA were performed. The stability of the complexes is studied by calculating the relative conformational energy of the cis-DP-DNA complexes with molecular mechanics (MM) and the intrinsic binding energy, which is the relative binding energy for ligand replacement in the presence of the substituents R with quantum mechanics. In the model, the receptor site geometry and the conformation of the DNA is changed little in the accommodation of the series of monosubstituted diammines. These diammines bind to one family of DNA conformations, denoted as IC in a previous study, and this suggests that a common conformational feature in the DNA may exist to explain the smooth trend in activity. The slight increase in van der Waals energy resulting from an increasing number of atoms in the substituents is countered by a larger decrease in the ligand replacement energy as the substituent increases in size. This overall decrease in relative energy is consistent with the slight decrease in activity as the substituent size increases.
本文展示了关于取代顺式铂（II）二胺（cis-DP）与DNA结合的研究结果。对一系列顺式-Pt(NH2R)2(+2)（其中R = H、CH3、环丙基、环丁基和环戊基）在DNA五聚体双链体的方形平面复合物中与两个相邻链内鸟嘌呤碱基的N7(G)原子进行了计算机建模。通过用分子力学（MM）计算顺式-DP-DNA复合物的相对构象能以及用量子力学计算在取代基R存在下配体置换的相对结合能（即内在结合能）来研究复合物的稳定性。在该模型中，在容纳一系列单取代二胺的过程中，受体位点的几何形状和DNA的构象变化不大。这些二胺与先前研究中标记为IC的一类DNA构象结合，这表明DNA中可能存在一个共同的构象特征来解释活性的平滑趋势。随着取代基中原子数的增加，范德华能略有增加，但随着取代基尺寸的增加，配体置换能有更大幅度的降低，从而抵消了这种增加。相对能量的总体降低与随着取代基尺寸增加活性略有降低是一致的。
