ACRIDINE MUTAGENS AND DNA STRUCTURE.
ACRIDINE MUTAGENS AND DNA STRUCTURE.
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吖啶诱变剂和 DNA 结构。
DOI：
10.1002/jcp.1030640403
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发表时间：
1964
影响因子：
--
通讯作者：
L. Lerman
中科院分区：
文献类型：
--
作者：
L. Lerman
通过对沉淀、低角度x射线散射、流动二色性、流动偏振荧光和化学反应性的研究确定了一些独立的关键结构参数，这些参数为吖啶化合物在两个其他顺序的碱基对之间插入提供了证据，并要求拒绝各种替代假设。结合需要局部解扭和双螺旋的延伸，这与正常的结构和结合参数是相容的。由于插层分子不容易受到亲电攻击，因此它们的化学反应性会发生实质性的变化，这一预期已被反应速率研究证实。应用极低剪切粘度法对稀DNA溶液粘度增强与插层关系的研究进行了扩展。结果与先前的测量结果一致，在可插层阳离子结合时观察到增强，而其他的则产生轻微的减弱。双螺旋结构明显稳定，热转变温度显著升高。插入到聚A和聚U之间形成的多核糖核苷酸配合物中，使双螺旋结构比三螺旋结构稳定得多。虽然插入似乎是插入-删除型致突变性的先决条件，但吖啶结构并不是必需的，也不是所有的插入分子都具有致突变性。
A number of independent critical structural parameters, which have been determined by studies on sedimentation, low angle X-ray scattering, flow dichroism, flow-polarized fluorescence, and chemical reactivity, provide the evidence for intercalation of the acridines between two otherwise sequential base pairs, and require the rejection of various alternative hypotheses. The binding requires a local untwisting and extension of the double helix, which is found to be compatible with the normal structural and bonding parameters. The expectation of a substantial alteration in the chemical reactivity of intercalated molecules because of their inaccessibility to electrophilic attack has been verified by reaction rate studies. Study of the relation between viscosity enhancement in dilute DNA solutions and intercalation has been extended using very low shear viscometry. The results agree with the earlier measurements in that the enhancement is observed with the binding of intercalatable cations, while others yield a slight diminution. A pronounced stabilization of the double helix is found, corresponding to a substantially raised thermal transition temperature. Intercalation into polyribonucleotide complexes formed between poly A and poly U renders the double helix substantially more stable than the triple. While intercalation seems to be prerequisite for mutagenicity of the insertion-deletion type, the acridine structure is not essential, nor are all intercalating molecules mutagenic.