Structure-specific recognition of quadruplex DNA by organic cations: Influence of shape, substituents and charge

Structure-specific recognition of quadruplex DNA by organic cations: Influence of shape, substituents and charge
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DOI:
10.1016/j.bpc.2006.06.006
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发表时间:
2007-03-01
影响因子:
3.8
通讯作者:
Wilson, W. David
Wilson, W. David
中科院分区:
生物学4区
文献类型:
--
作者:
White, Elizabeth W.;Tanious, Farial;Wilson, W. David

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将核酸的结构特异性识别与有限序列读取相结合是一种很有前途的方法,可以减少识别单元的大小,从而实现控制功能所需的选择性和结合亲和力。最近已经证明,有机阳离子可以以结构特异性的方式靶向g -四重体DNA结构。四联体的结构目标包括g -四联体堆叠柱的平面端面和四个凹槽。它们提供了相对于双工DNA不同的几何形状和官能团。我们利用表面等离子体共振和等温滴定量热法表明,一系列四重体末端堆叠分子对人类端粒DNA的结合亲和力和选择性对化合物形状、取代基类型和位置都很敏感。ITC结果表明,结合主要是由焓驱动的。圆二色性也被用来鉴定一组结构上相关的化合物,选择性地靶向四重凹槽。(c) 2006 Elsevier B.V.版权所有
Combining structure-specific recognition of nucleic acids with limited sequence reading is a promising method to reduce the size of the recognition unit required to achieve the necessary selectivity and binding affinity to control function. It has been demonstrated recently that G-quadruplex DNA structures can be targeted by organic cations in a structure-specific manner. Structural targets of quadruplexes include the planar end surfaces of the G-tetrad stacked columns and four grooves. These provide different geometries and functional groups relative to duplex DNA. We have used surface plasmon resonance and isothermal titration calorimetry to show that binding affinity and selectivity of a series of quadruplex end-stacking molecules to human telomeric DNA are sensitive to compound shape as well as substituent type and position. ITC results indicate that binding is largely enthalpy driven. Circular dichroism was also used to identify a group of structurally related compounds that selectively target quadruplex grooves. (c) 2006 Elsevier B.V. All rights reserved.