Interactions of molecules with nucleic acids. IV. Binding energies and conformations of acridine and phenanthridine compounds in the two principal and in several unconstrained dimer‐duplex intercalation sites
Interactions of molecules with nucleic acids. IV. Binding energies and conformations of acridine and phenanthridine compounds in the two principal and in several unconstrained dimer‐duplex intercalation sites
复制标题
IV. 吖啶和菲啶化合物在两个主体和几个不受约束的二聚体双链体嵌入位点的结合能和构象。
作者：
K. J. Miller;R. Brodzinsky;S. Hall
计算了9-氨基吖啶、前列腺素、N-甲基菲和乙锭在理论上确定的B-DNA插入位(I位和II位)和非限制性二聚体-双链位上的结合位置和相对最小结合能。这些化合物对B-DNA中I位的选择与对除乙锭外的所有情况下闭合环状DNA解旋角研究的理论解释一致，而乙锭则被预测为选择II位。在不受约束的二聚双链单元中，吖啶类和乙锭最稳定的结合位置与二核苷单磷酸单元插层络合物的实验结果一致。研究了Watson-Crick配对的碱基对专一性。插层络合物的能量被划分为ΔE23和ΔEin，前者是将B-DNA中的bp2和bp3开放到一个位点所需的能量，后者是当自由分子嵌入时能量变化。ΔE23强烈依赖于碱基对序列，而所研究的四个分子的ΔEIN不依赖于碱基序列。三个最稳定的序列含有(嘧啶)对(嘌呤)单元，这为与这些单元排他性地形成插层络合物晶体提供了理论基础。尽管有这种选择性，对于这三个单元，GṁC和AṁT碱基对的分布是相等的，并且随着包括更不稳定的序列而持续存在。因此，特异性来自碱基对和2‘-脱氧核糖5’-单磷酸骨架之间的相互作用，而不是发色团和DNA之间的相互作用。
The binding positions and relative minimum binding energies are calculated for complexes of 9‐aminoacridine, proflavine, N‐methylphenanthridinium, and ethidium in theoretically determined intercalation sites in B‐DNA (sites I and II) and in unconstrained dimer‐duplex sites. The selection of site I in B‐DNA by these compounds agrees with the theoretical interpretation of studies of unwinding angles in closed circular DNA in all cases but ethidium, which is predicted to select site II. The most stable binding positions of the acridines and ethidium in unconstrained dimer‐duplex units agree with experimental results of intercalation complexes of dinucleoside monophosphate units. Base‐pair specificity for Watson‐Crick pairing is examined. The energy of an intercalation complex is partitioned into ΔE23, the energy required to open base pairs BP2 and BP3 in B‐DNA to a site, and ΔEIn, the energy change when a free molecular intercalates. ΔE23 depends strongly on the base‐pair sequence, whereas ΔEIn for the four molecules studied does not. The three most stable sequences contain (pyrimidine)p(purine) units, and this provides a rationale for the exclusive formation of crystals of intercalation complexes with these units. In spite of this selectivity, the distribution of GṁC and AṁT base pairs is equal for these three units and persists as the more unstable sequences are included. Therefore, specificity arises from the interaction between the base pairs and the 2′‐deoxyribose 5′‐monophosphate backbone for the opening of B‐DNA to an intercalation site and not from the interaction between the chromophore and the DNA.