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首页> 外文期刊>Biochemistry >DISTAMYCIN A COMPLEXATION WITH A NUCLEIC ACID TRIPLE HELIX
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DISTAMYCIN A COMPLEXATION WITH A NUCLEIC ACID TRIPLE HELIX

机译：地西霉素与核酸三螺旋的络合物

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The interaction of the minor groove binding drug distamycin with the T-A-T triple helix and the A-T double helix was studied using circular dichroism spectroscopy and thermal denaturation. The triple helix was made by the oligonucleotide (dA)(12)-x-(dT)(12)-x-(dT)(12), where x is a hexaethylene glycol chain bridged between the S'-phosphate of one strand and the 5'-phosphate of the following strand. This oligonucleotide is able to fold back on itself to form a very stable tripler. Changing the conditions allows the same oligonucleotide to be in a duplex form with a dangling arm. Circular dichroism spectroscopy demonstrates that the distamycin A molecule can bind to the triple-stranded form of this oligonucleotide. Spectral analysis shows that the bound distamycin exhibits a conformation and an environment slightly different from those which are observed when the drug is bound to the corresponding double-stranded structure. Furthermore, a second type of complex which is observed in the double-strand binding (two stacked distamycins in the minor groove) is not observed with the triple-stranded host. When distamycin is added to the tripler made of unbridged chains (dA)(12)+2(dT)(12), the tripler dissociates to give a double-stranded structure. Thermal denaturation experiments demonstrate that distamycin binding destabilizes the tripler whereas it stabilizes the duplex. These results are compared with those obtained by the same experimental approaches on other minor groove binding drugs.
机译：使用圆二色性光谱和热变性研究了小沟结合药物distamycin与T-A-T三螺旋和A-T双螺旋的相互作用。三螺旋是由寡核苷酸（dA）（12）-x-（dT）（12）-x-（dT）（12）制成的，其中x是在一条链的S'-磷酸之间桥接的六甘醇链下一条链的5'-磷酸。该寡核苷酸能够向后折叠以形成非常稳定的三聚体。改变条件允许相同的寡核苷酸成为带有悬臂的双链体形式。圆二色性光谱表明，双霉素A分子可以结合该寡核苷酸的三链形式。光谱分析表明，结合的他霉素显示的构象和环境与将药物结合到相应的双链结构时观察到的构象和环境略有不同。此外，在三链宿主中未观察到在双链结合中观察到的第二种复合物（在小沟中有两个堆叠的二霉素）。当将地他霉素添加到由未桥连的链（dA）（12）+2（dT）（12）制成的三链体中时，该三链体解离形成双链结构。热变性实验表明，双霉素的结合使三链体不稳定，而使双链体稳定。将这些结果与通过其他小沟结合药物的相同实验方法获得的结果进行比较。

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