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通过吖啶橙识别三种不同的人类端粒 G-四链体构象。

Recognize three different human telomeric G-quadruplex conformations by quinacrine.

机构信息

National Laboratory for Molecular Sciences, Center for Molecular Sciences, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, PR China.

出版信息

Analyst. 2012 Feb 21;137(4):862-7. doi: 10.1039/c2an15870a. Epub 2012 Jan 5.

Abstract

Recognition of different human telomeric G-quadruplex structures has been a very important task for developing anti-cancer drug design. However, it also is a very challenging question since multiple conformational isomers of telomeric G-quadruplexes coexist under some conditions. Here, three different conformations including parallel, antiparallel, and mixed-type telomeric G-quadruplex structures have been well recognized by quinacrine (QNA) through monitoring its absorption, fluorescence, and fluorescence lifetime spectra. The multiple structures of H22 G-quadruplexes under physiological K(+) conditions could also be easily determined to coexist as mixed-type and antiparallel G-quadruplexes. The recognition mechanism based on the different binding affinity and binding sites has been further elucidated by association with the nuclear magnetic resonance (NMR) results.

摘要

识别不同的人类端粒 G-四链体结构对于开发抗癌药物设计一直是一项非常重要的任务。然而,由于在某些条件下端粒 G-四链体的多种构象异构体共存,这也是一个极具挑战性的问题。在这里,通过监测吖啶橙(QNA)的吸收、荧光和荧光寿命光谱,已经很好地识别了三种不同的构象,包括平行、反平行和混合型端粒 G-四链体结构。在生理 K(+)条件下,H22 G-四链体的多种结构也可以很容易地确定为混合型和反平行 G-四链体共存。通过与核磁共振(NMR)结果相关联,进一步阐明了基于不同结合亲和力和结合位点的识别机制。

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