Sequence and Chiral Selectivity of Drug-DNA Interactions Revealed by Force Spectroscopy

Sequence and Chiral Selectivity of Drug-DNA Interactions Revealed by Force Spectroscopy
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DOI:
10.1002/anie.201407093
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发表时间:
2014-12-15
影响因子:
16.6
通讯作者:
Xu, Shoujun
Xu, Shoujun
中科院分区:
化学1区
文献类型:
--
作者:
Hu, Qiongzheng;Xu, Shoujun

文献摘要

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差示结合力已被用于精确地表征药物分子与DNA双链体结合的机械效应。利用力诱导剩余磁化强度谱(FIRMS)测量的高分辨率结合力能够区分不同手性药物分子与不同序列DNA的结合行为。力谱首次揭示了Hg ~(2+)和道诺霉素的序列特异性,其结果与其他技术得到的结果一致。此外,D,L-延胡索乙素的两种异构体对两种不同的DNA序列表现出选择性。这种方法的一个特别有用的特点是,所研究的小分子不需要任何标记。
Differential binding force has been used to precisely characterize the mechanical effect of a drug molecule binding to a DNA duplex. The high-resolution binding forces measured by the force-induced remnant magnetization spectroscopy (FIRMS) enable the binding behavior of drug molecules with different chirality and DNA of various sequences to be distinguished. The sequence specificity of Hg2+ and daunomycin was revealed by force spectroscopy for the first time, and the results are consistent with those obtained by other techniques. Furthermore, the two isomers of D,L-tetrahydropalmatine showed selectivity for two different DNA sequences. One particular useful feature of this approach is that the small molecules under study do not require any labels.