The Spermine-Bisaryl Conjugate as a Potent Inducer of B- to Z-DNA Transition
The Spermine-Bisaryl Conjugate as a Potent Inducer of B- to Z-DNA Transition
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DOI：
10.1002/chem.201000947
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Sasaki, Shigeki
中科院分区：
文献类型：
--
作者：
Doi, Issei;Tsuji, Genichiro;Sasaki, Shigeki
含有交替的嘌呤和嘧啶重复序列的DNA有可能采用Z-DNA结构，这是除了A-DNA和B-DNA之外研究得很好的结构之一。尽管已经提出了许多分子模型来解释B-Z转变的机制，但关于这种转变的机制和生理作用仍在继续讨论。在本研究中，我们发现双(2-萘基)-马来酰亚胺-精胺共轭化合物(3c)在低盐浓度下表现出显著的引起d(CGCG)(2)的B-GT；Z跃迁的能力。用等温滴定量热法(ITC)证明了3C诱导的B->；Z相变既是热有利的，也是有利的。该配体可能影响B-DNA的脱水，从而导致B->；Z转变。有趣的是，在配体的存在下，在pH依赖的转变中观察到了B型和Z型之间的中间CD。本研究设计的配体的独特结构和性质将有助于Z-DNA的研究。
DNA containing alternating purine and pyrimidine repeats has the potential to adopt the Z-DNA structure, one of the well-studied structures besides A- and B-DNA. Despite a number of molecular models that have been proposed to explain the mechanism for B -> Z transition, there is continued discussion on the mechanism and physiological role of this transition. In this study, we have found that the bis(2-naphthyl)-maleimide-spermine conjugate (3c) exhibits a remarkable ability to cause the B -> Z, transition of d(CGCGCG)(2) at low salt concentrations. Using isothermal titration calorimetry (ITC) we show that the B -> Z transition induced by 3c is both enthalpically and entropically favorable. The ligand might effect the dehydration of B-DNA, which leads to the B -> Z transition. Interestingly, an intermediate CD between the B and Z forms was observed in the pH-dependent transition in the presence of the ligand. The unique structure and characteristics of the ligand designed in this investigation will be useful for the study of Z-DNA.