Natural and synthetic double-stranded DNA binding studies of macrocyclic tetraamine zinc(II) complexes appended with polyaromatic groups
Natural and synthetic double-stranded DNA binding studies of macrocyclic tetraamine zinc(II) complexes appended with polyaromatic groups
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带有多芳香族基团的大环四胺锌 (II) 配合物的天然和合成双链 DNA 结合研究
DOI：
10.1007/s007750050329
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Eiichi Kimura
中科院分区：
文献类型：
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作者：
E. Kikuta;N. Katsube;Eiichi Kimura
大环四胺配合物（1,4,7,10-四氮杂环十二烷，环烯）附加一个或两个芳基甲基(s)[（4-喹啉）甲基-，1,7-二（4-喹啉）甲基-，（1-萘基）甲基-，1,7-二（1-萘基）甲基-，和（9-acridinyl）甲基环烯]与双链小牛胸腺DNA和合成DNA[聚（dA）·聚（dT），聚（dA-dT）2，聚（dI）·聚（dC），聚（dI-dC）2，聚（dG）·聚（dC），和poly(dG-dC)2]已经通过分光光度法、Tm测量和这些dna定向转录的体外抑制来检测。用天然DNA和合成DNA进行滴定，观察到配合物的垂坠芳香吸收光谱有不同的异色和深色效应。在含0.1 M Na+的10 mM EPPS （pH 8.0）中，测定了25°C下的结合常数Kapp(=[结合环素衍生物]/[未结合环素衍生物][DNA磷酸盐]M - 1)，并与相应的无Zn2+配体进行了比较。结果表明，与相应的双质子化配体相比，Zn2+环环配合物与DNA的相互作用更强，导致了更强的垂芳环堆叠。Zn2+ -（9-吖啶酰基）甲基环素与小牛胸腺DNA的结合是由at选择性的次要凹槽结合剂二霉素竞争的，而不是由主要凹槽结合剂甲基绿竞争的。在过量的Zn2+- (9-acridinyl)甲基环素与聚（dA）·聚（dT）的不寻常相互作用中，Zn2+-环素片段进入小凹槽与胸腺嘧啶的去质子化亚胺形成配位键，导致聚（dA）·聚（dT）双相的破坏。Zn2+ -（9-吖啶基）甲基环素抑制了含胸腺嘧啶RNA聚合酶的dna定向转录。以poly（dA）·poly（dT）或poly(dA-dT)2为模板时，50%的转录抑制浓度（IC50）为22 ~ 45 μM，以poly(dG-dC)2为模板时，IC50值为110 μM。
Abstract The characteristic binding mode of zinc(II) complexes of macrocyclic tetraamines (1,4,7,10-tetraazacyclododecane, cyclen) appended with one or two arylmethyl group(s) [(4-quinolyl)methyl-, 1,7-bis(4-quinolyl)methyl-, (1-naphthyl)methyl-, 1,7-bis(1-naphthyl)methyl-, and (9-acridinyl)methyl-cyclen] to double-stranded calf thymus DNA and synthetic DNAs [poly(dA)·poly(dT), poly(dA-dT)2, poly(dI)·poly(dC), poly(dI-dC)2, poly(dG)·poly(dC), and poly(dG-dC)2] has been examined by spectrophotometric methods, Tm measurement, and inhibition of these DNA-directed transcriptions in vitro. Various hypochromic and bathochromic effects on the pendant aromatic absorption spectra of the complexes were observed in titration with the native and synthetic DNA. The binding constants Kapp (=[bound cyclen derivatives]/[unbound cyclen derivatives][DNA phosphates] M–1), at 25 °C in 10 mM EPPS (pH 8.0) containing 0.1 M Na+, were determined and compared with those of the corresponding Zn2+-free ligands. The results showed that the Zn2+-cyclen complexes interact with the DNA more strongly than the corresponding diprotonated ligands, leading to a stronger stacking of the pendant aromatic rings. The binding of Zn2+–(9-acridinyl)methyl-cyclen to calf thymus DNA was competed by an AT-selective, minor groove binder, distamycin, but not by a major groove binder, methyl green. In an unusual interaction of excess Zn2+–(9-acridinyl)methyl-cyclen with poly(dA)·poly(dT), the Zn2+-cyclen moiety went into the minor groove to make coordination bonds with the deprotonated imides of the thymines, resulting in disruption of the poly(dA)·poly(dT) duplex. Thymine-containing DNA-directed transcription with Escherichia coli RNA polymerase in vitro was inhibited by the Zn2+–(9-acridinyl)methyl-cyclen. The 50% inhibition concentrations of the transcription (IC50) were 22–45 μM with poly(dA)·poly(dT) or poly(dA-dT)2 as templates, while with poly(dG-dC)2 as a template the IC50 value was 110 μM.