Miller K J, Taylor E R, Basch H, Krauss M, Stevens W J
Department of Chemistry, Rensselaer Polytechnic Institute, Troy, NY 12181.
J Biomol Struct Dyn. 1985 Jun;2(6):1157-71. doi: 10.1080/07391102.1985.10507630.
The binding of cis-Pt(NH3)2B1B2 to the bases B1 and B2, i.e., guanine (G), cytosine (C), adenine (A), and thymine (T), of DNA is studied theoretically. The components of the binding are analyzed and a model structure is proposed for the intrastrand binding to the dB1pdB2 sequence of a kinked double helical DNA. Quantum mechanical calculations of the ligand binding energy indicates that cis-Pt(NH3)2(+2) (cis-PDA) binds to N7(G), N3(C), O2(C), O6(G), N3(A), N7(A), O4(T) and O2(T) in order of decreasing binding energy. Conformational analysis provides structures of kinked DNA in which adjacent bases chelate to cis-PDA. Only bending toward the major groove allows the construction of acceptable square planar complexes. Examples are presented for kinks of -70 degrees and -40 degrees at the receptor site to orient the base pairs for ligand binding to B1 and B2 to form a nearly square planar complex. The energies for complex formation of cis-PDA to the various intra-strand base sites in double stranded DNA are estimated. At least 32 kcal/mole separates the energetically favorable dGpdG.cis-PDA chelate from the dCpdG.cis-PDA chelate. All other possible chelate structures are much higher in energy which correlates with their lack of observation in competition with the preferred dGpdG chelate. The second most favorable ligand energy occurs with N3(C). A novel binding site involving dC(N3)pdG(N7) is examined. Denaturation can result in an anti----syn rotation of C about its glycosidic bond to place N3(C) in the major groove for intrastrand binding in duplex DNA. This novel intrastrand dCpdG complex and the most favored dGpdG structure are illustrated with stereographic projections.
对顺式二氯二氨合铂（cis-Pt(NH3)2B1B2）与DNA的碱基B1和B2，即鸟嘌呤（G）、胞嘧啶（C）、腺嘌呤（A）和胸腺嘧啶（T）的结合进行了理论研究。分析了结合的组成部分，并提出了一种模型结构，用于链内与扭结双螺旋DNA的dB1pdB2序列的结合。配体结合能的量子力学计算表明，顺式二氯二氨合铂（cis-Pt(NH3)2(+2)，顺式PDA）按结合能递减顺序与N7(G)、N3(C)、O2(C)、O6(G)、N3(A)、N7(A)、O4(T)和O2(T)结合。构象分析提供了扭结DNA的结构，其中相邻碱基与顺式PDA螯合。只有向大沟弯曲才能构建出可接受的正方形平面配合物。给出了受体位点处-70度和-40度扭结的例子，以使碱基对定向，便于配体与B1和B2结合，形成近乎正方形平面的配合物。估计了顺式PDA与双链DNA中各种链内碱基位点形成配合物的能量。能量上有利的dGpdG.cis-PDA螯合物与dCpdG.cis-PDA螯合物之间至少相差32千卡/摩尔。所有其他可能的螯合结构能量都高得多，这与它们在与首选的dGpdG螯合物竞争中未被观察到有关。第二有利的配体能量出现在N3(C)处。研究了一个涉及dC(N3)pdG(N7)的新结合位点。变性可导致C围绕其糖苷键发生反式-顺式旋转，使N3(C)位于大沟中，用于双链DNA中的链内结合。用立体投影展示了这种新的链内dCpdG配合物和最有利的dGpdG结构。
